Kiedis was born in Grand Rapids, Michigan, to Margaret "Peggy" (Noble) and actor John Michael Kiedis, known professionally as Blackie Dammett. His paternal grandfather's family emigrated from Lithuania in the early 1900s; the remainder of his ancestry includes English, French, Dutch, and Mohican. In 1966, when he was three years old, his parents divorced. He was raised by his mother in Grand Rapids, later his mother remarried and had two more children- Anthony’s half sisters. Each summer, he would visit his father in Hollywood for two weeks, a time during which the two would bond. He idolized his father, and recalled, "Those trips to California were the happiest, most carefree, the-world-is-a-beautiful-oyster times I'd ever experienced." In 1974, when Kiedis was twelve years old, he moved to Hollywood to live with his father full-time. His father was a struggling actor who sold drugs, which had a significant impact on Kiedis, as the two would often use marijuana and cocaine together. Kiedis accidentally tried heroin for the first time at age 14, mistaking the substance for cocaine. Through his father Blackie, Kiedis, who worked under the stage name of Cole Dammett, landed his first acting role appearing as Sylvester Stallone's character's son in the 1978 film, F.I.S.T. That same year he would land two more acting jobs, one being on an ABC Afterschool Special and the other an appearance in the film, Jokes My Folks Never Told Me.

Using the stage name Cole Dammett (adapted from his father's stage name, Blackie Dammett), Kiedis landed a number of small roles in television and film as a teenager in the late 1970s. His early credits include F.I.S.T. and the 1978 ABC Afterschool Special It's a Mile from Here to Glory. Resuming his acting work in the 1990s, Kiedis appeared in the 1991 Keanu Reeves and Patrick Swayze vehicle Point Break playing Tone, a Surfer. The Chase, a 1994 movie starring Charlie Sheen as an estranged man trying to escape the cops with a young woman he kidnapped, had Flea and Kiedis playing metalheads who chase Sheen's character in a 4 × 4 truck and end up crashing.

Kiedis also met Future bandmate Slovak after seeing him perform with his band Anthym. After the show, Slovak invited Kiedis to his house for a snack. Kiedis later described the experience in his autobiography Scar Tissue: "Within a few minutes of hanging out with Hillel, I sensed that he was absolutely different from most of the people I'd spent time with...He understood a lot about music, he was a great visual Artist, and he had a sense of self and a calm about him that were just riveting." Slovak, Kiedis, and Flea became best friends and often used LSD, heroin, cocaine, and speed recreationally. Despite his frequent drug use, he excelled in school, often receiving straight A grades. In June 1980, Kiedis graduated with honors from high school. That August, he enrolled at the University of California, Los Angeles to study writing. However, he dropped out at the beginning of his second year due to his worsening addiction to cocaine and heroin.

Following the group's first show at The Rhythm Lounge, the owner of the bar asked them to return, but with two songs instead of one. After several more shows, and the addition of several songs to their repertoire, the band's name was changed to Red Hot Chili Peppers. The band's concert repertoire grew to ten songs as a result of months of playing at local nightclubs and bars. At a performance at a strip club in Hollywood called Kit Kat Club, the band members performed wearing only socks on their penises, an idea formed by Kiedis. This gained the band notoriety, and club owners even began booking the group on the condition that they would perform in this manner. The Red Hot Chili Peppers entered Bijou Studios to record a demo tape and subsequently secured a record deal with EMI. Irons and Slovak however, decided to leave the Red Hot Chili Peppers in order to pursue a "more serious" Future with rock band What Is This? Kiedis ultimately respected the decision, but felt the band would be lost without them. Kiedis and Flea hired Drummer Cliff Martinez from The Weirdos and Guitarist Jack Sherman to fill Iron's and Slovak's places, respectively. Andy Gill, formerly of Gang of Four, agreed to produce their first album, 1984's The Red Hot Chili Peppers. Gill and Sherman clashed with Kiedis and Flea; they continuously argued over music style, sound, and the album's production. Sherman was fired from the band following the tour and replaced by a returning Slovak.

Funk musician George Clinton was hired to produce the band's second album, Freaky Styley, as Slovak returned on guitar. The strong chemistry between Clinton and the Chili Peppers was felt instantly. Freaky Styley was released in August 1985. It received only a bit more attention than The Red Hot Chili Peppers with roughly 75,000 copies sold by year's end. The band hired Michael Beinhorn, their last resort among potential producers, to work on their next album. What Is This? had finally disbanded, and Irons returned to the Chili Peppers in mid-1986 after Martinez was fired. Flea, Slovak and Kiedis especially were involved in heavy drug use and their relationships became strained. Flea recalled that "it began to seem ugly to me and not fun; our communication was not healthy". Kiedis became dependent on heroin, leaving Flea and Slovak to work on much of the album's material by themselves. Both Kiedis and Slovak struggled with debilitating heroin addictions, which grew worse as the band was preparing to record The Uplift Mofo Party Plan. Due to his addiction, Kiedis lacked the motivation to contribute to the band musically, and appeared at rehearsal "literally asleep". He was asked to leave the band in order to undergo drug rehabilitation. During that time, the band won the LA Weekly Band of the Year award, which prompted Kiedis to quit using heroin cold Turkey. He visited his mother in Michigan for guidance, who drove him to drug rehabilitation immediately after picking him up from the airport upon seeing his unhealthy appearance. Kiedis checked into a Salvation Army rehabilitation clinic in Grand Rapids, an experience which he initially detested until he noted that the other people in the clinic were understanding of his struggles and were trying to help him. He moved in with his mother after twenty days at the clinic, a time which marked the first time he was completely abstinent from drugs since he was eleven years old. After Kiedis completed his stint in rehabilitation, he felt a "whole new wave of enthusiasm" due to his sobriety and wrote the lyrics to a new song titled "Fight Like a Brave" on the FLIGHT home.

He rejoined the Red Hot Chili Peppers in Los Angeles to record the album. Upon returning home, he began dating Actress Ione Skye, whom Flea had met while appearing with her in the 1987 science fiction film Stranded. Although Kiedis had recently become clean, his withdrawal symptoms increased and affected his musical contributions to the group. After fifty days of sobriety, Kiedis decided to take drugs again as a one-time attempt to celebrate his new music, which led to his resumed addiction. The recording process for the album became difficult as Kiedis would often disappear to seek drugs. Producer Michael Beinhorn recalled that "There were points in pre-production where I really thought the record wasn't gonna get made." Kiedis felt "excruciating pain and guilt and shame" when he would miss a recording session so he would try to write lyrics while searching for drugs; although the band members were upset by his drug use and frequent disappearances, they were impressed with his musical output at the time.

Kiedis has battled drug addiction, including heroin and cocaine, throughout his life. Since his father was an addict, Kiedis was constantly exposed to drug-using and drug-dealing behavior while growing up. Some of Kiedis's early drug use came from substances he got from his father, including marijuana, which he first smoked when he was 12 years old. He used drugs for years, including during the formation of the band, where other members were also using. A few years into the band's career, he was briefly fired due to his heavy drug use, and at times it got so bad that he failed to show up to some of the band's performances. One night, Kiedis decided to go out and score drugs, which made him miss a performance so the band replaced him with singer Keith Morris. He tried to get clean after Red Hot Chili Peppers Guitarist Hillel Slovak died of a heroin overdose (specifically using the method of speedballing) on June 25, 1988, saying he would never shoot up again. He entered rehab and ended up staying clean for five years, but he relapsed in 1994, causing a major delay in the release of the band's 1995 album, One Hot Minute, and he kept using on and off over the next six years.

His early vocal style with the band primarily consisted of rapping. On Mother's Milk (1989), Kiedis wrote more melody-driven songs, rather than the basic rhythm and beat style of funk. The first song where Kiedis employed his new melodic style was "Knock Me Down". The melody was actually shaped and performed by Guitarist John Frusciante. Upon joining the band, Frusciante sang lead vocals on the song along with Kiedis. Blood Sugar Sex Magik in 1991 still saw Kiedis rapping, but he also started singing in songs such as "Under the Bridge", "Breaking the Girl", and "I Could Have Lied". Over the years, Kiedis grew to favor singing over rapping. Kiedis has had many vocal coaches, but none of them had helped him sing "well." In fact, it was not until 1999's Californication that he felt he could take full control of his voice while singing.

Like with Christie, many of Kiedis' former relationships have inspired his writing and lyrics. Kiedis had a brief relationship in 1990 with singer Sinéad O'Connor who inspired him to write "I Could Have Lied" on 1991's Blood Sugar Sex Magik while a brief fling with Spice Girls singer Melanie "Sporty Spice" Chisholm inspired "Emit Remmus" from 1999's Californication. Yohanna Logan, with whom Kiedis dated on and off from 1998-2003, served as a positive inspiration on songs from the Californication era such as the outtake "Fat Dance" while their breakup inspired 2002's By the Way album and many of its song lyrics.

The band sought to record their next album Blood Sugar Sex Magik in an unconventional setting, believing it would enhance their creative output. The band's Producer Rick Rubin suggested the mansion Magician Harry Houdini once lived in, to which they agreed. A crew was hired to set up a recording studio and other equipment required for production in the house. The band decided that they would remain inside the mansion for the duration of recording, though Smith, convinced the location was haunted, refused to stay. During this stage, Kiedis began to write about anguish, and the self-mutilating thoughts he would experience as a result of his heroin and cocaine addiction. Chili Peppers Producer Rick Rubin stumbled upon one of Kiedis's poems that would become the lyrics to "Under the Bridge", and suggested Kiedis show it to the rest of the band. Kiedis was apprehensive because he believed the lyrics to be "too soft" and unlike the band's style. After singing the verse to Frusciante, they began structuring the song the next day. The two worked for several hours arranging chords and melodies until they both agreed it was complete. The song later became a major hit, peaking at number two on the Billboard 100. When Blood Sugar Sex Magik was released on September 24, 1991, it received an overwhelmingly positive critical response. The album peaked at number three on the Billboard Hot 200, and went on to sell over seven million copies in the U.S. alone. The album's ensuing tour was critically acclaimed—the Chili Peppers commonly performed shows with over twenty thousand in attendance. Seattle-based grunge band Nirvana also toured with them during the West Coast leg of their United States tour. The massive attention the Chili Peppers started receiving caused Frusciante to feel extremely uncomfortable, and he abruptly quit the band during the Japanese leg of the album's tour. The band hired Guitarist Arik Marshall to complete the remaining tour dates. The band appeared live on the Grammy's ceremony with George Clinton's P-Funk collective and many others, performing a medley that included "Give It Away".

Months went by, and only small amounts of material were written leading Chad Smith to publicly announce that Kiedis was suffering from writer's block (something Kiedis denied). The rest of the recording was completed within the next month and their sixth album One Hot Minute was released in September 1995, featuring the band's new Guitarist Dave Navarro. The album was met with mixed reviews and was a major departure from the band's funk-rock sound. The tour to support the album was also met with mixed results. Chad Smith broke his arm prior to the launch of the U.S. tour in 1995 so it was delayed until early 1996. Near the tour's end, Kiedis was involved in a motorcycle accident which left him with a broken arm. The tour ended with the band's final set being cut short due to a massive Typhoon. 1997 was dubbed by the band the year of nothing.

In retaliation to being thrown off the festival shows, Mr. Bungle parodied the Red Hot Chili Peppers in Pontiac, Michigan on Halloween of 1999. Patton introduced each Mr. Bungle band member with the name of one of the Red Hot Chili Peppers, before covering the songs "Give It Away", "Around the World", "Under the Bridge" and "Scar Tissue", with Patton deliberately using incorrect lyrics. Mr. Bungle also satirized many of the mannerisms of the band, mocking heroin injections, deceased Guitarist Hillel Slovak and on-stage antics. Kiedis responded by having them removed from the 2000 Big Day Out festival in Australia and New Zealand. Kiedis said of the festival shows "I would not have given two fucks if they played there with us. But after I heard about [the] Halloween show where they mocked us, fuck him and fuck the whole band." Patton went on to claim that Kiedis' actions had "ruined" Mr. Bungle's career, while Bassist Trevor Dunn remarked "It really screwed us up. It screwed up my life in a personal way."

The animosity continued into the 2000s, with Dunn criticizing the Chili Peppers on his personal webpage, specifically their bass player Flea, stating, "Flea, in all seriousness, really isn't that good. I mean c'mon Red Hot Chili Peppers were vaguely interesting in the late 80s, but Christ they fucking suck, they suck". Patton was asked in 2010 about the festivals and his relationship with Kiedis. Patton said "It’s not worth talking about. I’ve no idea what it was about then and I don’t know now. But I bet we’d have a warm embrace if we saw each other now." In 2016, Trey Spruance reflected on the Mr. Bungle feud, stating that it was a "weird and unprofessional jealous vendetta from a huge successful band towards an industry pip-squeak."

In January 2001 friend and associate Guy Oseary (Guy O), as a birthday gift, arranged for Kiedis to collect a Rhodesian Ridgeback from breeders in the town of Julian, California. Kiedis named the dog Buster, after one of his favourite comedians, Buster Keaton.

On October 6, 2004, Kiedis published a memoir titled Scar Tissue, which he co-wrote with author Larry Sloman. The book was originally intended to be a collection of stories of his childhood drug use, but evolved into a complete autobiography. He further explained: "One would just kind of assume that with all the [drug] consumption that my memory would be a bit shoddy. But it's actually pretty lucid, and better than both of my parents', or any of my friends'. My friends tried to recount these same stories, and they were like, 'Wow, I don't ... were we there?'" The book was an international bestseller.

The formation and recording of Stadium Arcadium took place at "The Mansion", the former home of Harry Houdini where the Chili Peppers had recorded their 1991 breakthrough Blood Sugar Sex Magik. Kiedis noted that during the recording process of the album "everybody was in a good mood. There was very little tension, very little anxiety, very little weirdness going on and every day we showed up to this funky room in the Valley, and everyone felt more comfortable than ever bringing in their ideas." The album was released on May 9, 2006.

Kiedis has a son named Everly Bear born October 2, 2007, from a relationship with model Heather Christie which lasted from 2004 to 2008. Christie, who was 18 when they began dating (Kiedis was 41), served as an inspiration for his lyrics on the band's 2006 album Stadium Arcadium. Songs like "She's Only 18" and "Desecration Smile" were written directly about Christie.In March 2018, Kiedis and Christie were involved in a custody battle over Everly.

Following a hugely successful world tour to support Stadium Arcadium, the band decided to take an extended year long break from music in 2008. According to Kiedis, there was a collective decision "not [to] do anything Red Hot Chili Peppers-related for a minimum of one year. [...] We started in 1999, with the writing and the recording of Californication, and we didn't really stop until the tour ended last year. We were all emotionally and mentally zapped at the end of that run." During the break, Frusciante departed amicably with the band in July 2009 (although it wasn't publicly announced until December 2009). Josh Klinghoffer, a touring Guitarist for the Chili Peppers and often collaborator with Frusciante was hired as his replacement.

According to a post by Blackie on his Facebook page, the John Sayles script for the pilot episode was turned over to HBO on May 10, 2010. On October 14, 2011 it was announced that HBO was no longer interested in the series and that FX has picked up the rights to air the series. John Sayles, who wrote a script for the HBO pilot is no longer involved in the project. Entourage producers, Esther Dawson and Mike Chester will still produce the series and Kiedis will also co-produce the series along with Bram Sheldon. It is unknown if the series will still follow the relationship between Kiedis and his father Blackie or if the entire autobiography will be the focus of the series. In 2013, Dammett briefly mentioned the status of the series, which will be based on both Anthony and Dammett's biographies. Dammett stated the series is currently "mothballed" however he hopes they re-visit the project once the Chili Peppers wrap up their tour in 2013.As of 2017, the series appears to no longer be in the works.

He also organized the New American Music Union, a two-day summer music festival set for August 2008 in Pittsburgh, Pennsylvania. He has assembled a lineup of Musicians including Bob Dylan, The Raconteurs, Gnarls Barkley, The Roots, and a second stage featuring college bands. (The lineup did not include Kiedis or the Red Hot Chili Peppers.) In 2011, Kiedis, along with his son Everly, appeared in the documentary, Bob and the Monster. The documentary details the life and career of musician and drug counselor, Bob Forrest. On May 11, 2011, Anthony donated a MTV European Music Award that the band had previously won to help raise funds for ongoing relief in devastated areas of Japan, which was hit with an earthquake and tsunami in March 2011.

A failed two-year relationship with Australian model Helena Vestergaard, who was only 19 when they began dating in 2012 (he was 50), served as a major influence on his songwriting for the band's 2016 album, The Getaway which often has Kiedis questioning their relationship and the age difference between the two. “Lyrically, I’m embarrassed to say, but a two-year relationship that completely fell apart like a nuclear bomb just left me feeling pretty raw and available to the emotional universe for writing. So even though the relationship was a bit of a disaster, I feel that in some way I did get something out of it, which was about half the songs on this record,” Kiedis said.

Kiedis' father, Blackie Dammett, is an actor who has appeared in over 50 movies and television shows. Dammett's autobiography, Lords of the Sunset Strip, was released on March 31, 2013. Through Dammett, Kiedis also has a much younger half-brother. During the Chili Peppers June 25, 2017 show in Grand Rapids, Kiedis dedicated "Soul to Squeeze" to his father who was losing his battle with dementia. "My father is fixin’ to die and that’s OK. He's had a wild, great journey and a helluva colourful badass life but he’s sick and he’s going to die now. He’s pretty lost; he’s just a spirit but I would like for everyone just to take ten seconds to send him some love to send his spirit some love because pretty soon he will be sailing on and I would appreciate it if his hometown could send him love for a whole ten seconds of love. Let’s give it up. Ten! Thank you. Let’s do this tune. Appreciate it."

According to Mr. Bungle themselves, Kiedis had never met or spoken to anyone involved with the band aside from Mike Patton. Patton stated to The A.V. Club, "Our agent was in the process of booking these festivals, and it was becoming apparent that we'd landed some pretty good ones—one in France, another one in Holland, some big-name festivals. Turns out someone's holding a grudge! We were booted off several bills, specifically because Anthony Kiedis did not want us on the bill. He threatened to pull the Chili Peppers if Mr. Bungle was on the bill." In a separate interview, he also clarified that "the rest of the band doesn't care. It's something to do with Anthony." Mr. Bungle's Guitarist Trey Spruance added, "We were booked, months in advance, to do eleven festival dates in Europe. Come Summer, we get a call from the three biggest of those festivals, all of them the same day, saying that we can't play, because the headlining band retains the right to hire and fire whomever they wish. We found out it was the Red Hot Chili Peppers, so our manager called their manager to find out what the hell was going on, and their manager was very apologetic, and said, 'We're really sorry, we want you to know this doesn't reflect the management's position, or the band's for that matter, it's Anthony Kiedis who wants this.'"

In June 2015, Kiedis and his son Everly Bear, along with Cher and Willow Smith, were revealed to be the "new faces" of Marc Jacobs Fall 2015 ad campaign.

In a June 2016 interview, Kiedis stated that he at first regretted writing Scar Tissue saying “I did regret the book for a while as there was some pain caused then, I started seeing the long term positive reverberating. People were reading it in hospitals, in prisons and schools and it was having a positive effect. I realised that the whole point of writing that book wasn’t for me, but to show that somebody can go all the way down and come all the way back and have a productive, successful happy interesting life. And so whatever shame, pain or difficulty or discomfort I went through, then it was worth it because I get so many people coming up to me saying their kids had read it and got their act together because of it.” Kiedis has stated that due to the subject matter in his book, especially his reflections on his sexual relationships, that he hopes that his family hasn't read his book. “I have asked everyone in my family not to read the book.” Kiedis said.