In November 1983, manager Lindy Goetz struck a seven-album deal with EMI America and Enigma Records. Two weeks earlier however, What Is This? had also obtained a record deal with MCA. Slovak and Irons still considered the Red Hot Chili Peppers as only a side project and so in December 1983 they quit to focus on What Is This?. Instead of dissolving the band, Kiedis and Flea recruited new members. Cliff Martinez, a friend of Flea's and member from the punk band, The Weirdos, was the new replacement for Irons. The band held auditions for a new Guitarist but decided after a few practices that Weirdos Guitarist Dix Denney did not fit. Kiedis described the two final candidates, Mark Nine and Jack Sherman, respectively as a "hip avant-garde art school refugee" and a nerd looking guy with a combed-back Jewfro with an unknown background. Musically Sherman clicked right away with Flea and Martinez and was hired as Slovak's replacement.

The band released their eponymous debut album, The Red Hot Chili Peppers on August 10, 1984. Though the album did not set sales records, airplay on college radio and MTV helped to build a fan base, and the album ultimately sold 300,000 copies. Gang of Four Guitarist Andy Gill, who produced the album "didn't embrace [the band's] musical aesthetic or ideology, argued constantly with the band over the record's sound." Kiedis recalled, that "Andy's thing was having a hit at all costs, but it was such a mistake to have an agenda." Despite the misgivings of Kiedis and Flea, Gill pushed the band to play with a cleaner, crisper, more radio-friendly sound. The band was disappointed in the record's overall sound, feeling it was overly polished and as if it had "gone through a sterilizing Goody Two-shoes machine". The album included backing vocals by Gwen Dickey, the singer for the successful 1970s disco funk group Rose Royce. The band embarked on a grueling tour during which they performed sixty shows in sixty-four days. During the tour, continuing musical and lifestyle tension between Kiedis and Sherman complicated the transition between concert and daily band life. When the tour ended in October 1984, Sherman was fired. Hillel Slovak, who had just quit What Is This?, would re-join the band in early 1985.

George Clinton produced the next album, Freaky Styley (1985). Clinton combined various elements of punk and funk into the band's repertoire, allowing their music to incorporate a variety of distinct styles. The album featured Maceo Parker and Fred Wesley on many of the album's tracks. The band often indulged in heavy heroin use while recording the album, which influenced the lyrics and musical direction of the album. The band had a much better relationship with Clinton than with Gill, but Freaky Styley, released on August 16, 1985, also achieved little success, failing to make an impression on any chart. The subsequent tour was also considered unproductive by the band. Despite the lack of success, the band was satisfied with Freaky Styley; Kiedis reflected, that "it so surpassed anything we thought we could have done that we were thinking we were on the road to enormity." The band appeared in the 1986 movie Thrashin' (directed by David Winters and starring Josh Brolin) playing the song "Blackeyed Blonde" from Freaky Styley. During this time the band also appeared in the movie Tough Guys starring Burt Lancaster and Kirk Douglas performing the song "Set It Straight" at a Los Angeles nightclub.

In spring 1986, the band decided to begin work on their upcoming album. EMI gave the band a budget of $5,000 to record a demo tape, and the band chose to work with Producer Keith Levene, because he shared the band's interest in drugs. Levene and Slovak decided to put aside $2,000 of the budget to spend on heroin and cocaine, which created tension between the band members. Martinez' "heart was no longer in the band", but he did not quit, so Kiedis and Flea fired him. After the firing of Martinez in April 1986, original Drummer Jack Irons rejoined the band to Kiedis, Flea, and Slovak's great surprise, which marked the first time all four founding members were together since 1983. During the recording and subsequent tour of Freaky Styley, Kiedis and Slovak were dealing with debilitating heroin addictions. Due to his addiction, Kiedis "didn't have the same drive or Desire to come up with ideas or lyrics" and appeared at rehearsal "literally asleep". Flea, Slovak and Irons informed Kiedis to clean up his drug habit or be fired from the band.

Original Guitarist Slovak's style was strongly based on blues and funk. Slovak was primarily influenced by hard rock artists such as Jimi Hendrix, Kiss and Led Zeppelin. His playing method was highly based on improvisation, a style commonly used in funk music. He also was noted for his aggressive playing style; he would often play with such force, that his fingers would "come apart". Kiedis observed that his playing evolved during his time away from the group in What Is This?, with Slovak adopting a more fluid style featuring "sultry" elements as opposed to his original hard rock techniques. On The Uplift Mofo Party Plan (1987), Slovak experimented with genres outside of traditional funk music including reggae and speed metal. His guitar riffs would often serve as the basis of the group's songs, with the other members writing their parts to complement his guitar work. His melodic riff featured in the song "Behind the Sun" inspired the group to create "pretty" songs with an emphasis on melody. Kiedis describes the song as "pure Hillel inspiration". Slovak also used a talk box on songs such as "Green Heaven" and "Funky Crime", in which he would sing into a tube while playing to create psychedelic effects.

The Chili Peppers were again without a Drummer and were forced to hold open auditions. Denise Zoom, a friend of the band, suggested Chad Smith, claiming he was the best Drummer she had ever seen. The band agreed to audition Smith, but he was late and the last Drummer to audition. Kiedis recalled the first time he saw Smith by saying, "I spied this big lummox walking down the street with a really bad Guns N' Roses hairdo and clothes that were not screaming I've got style". Smith was a six-foot three-inch tall Drummer who, according to Flea, "lit a fire under our asses". From the moment they started jamming, Smith and Flea instantly found chemistry. Smith was a hard-hitting musician with whom the Chili Peppers believed they would create a strong relationship. Kiedis said the audition with Smith "left the band in a state of frenzied laughter, that we couldn't shake out of for a half an hour". Smith was so much different from the other three. Kiedis, Flea and Frusciante were heavily influenced by punk rock, whereas Smith's taste in heavy metal music and his biker appearance contrasted with their punk rock views. Kiedis informed Smith he would be hired on one condition: as an initiation to the band, Smith had to cut his long hair. He refused, though Kiedis was not about to argue with the much larger Smith. Smith was hired as the band's fourth Drummer on December 3, 1988.

Through the years, Kiedis' lyrics covered a variety of topics, which shifted as time progressed. Early in the group's career, Kiedis wrote mostly comical songs filled with sexual innuendos as well as songs inspired by friendship and the band members' personal experiences. However, after the death of his close friend and bandmate Hillel Slovak, Kiedis' lyrics became much more introspective and personal, as exemplified by the Mother's Milk (1989) song "Knock Me Down", which was dedicated to Slovak along with the Blood Sugar Sex Magik (1991) song, "My Lovely Man".

In 1990, the band appeared in PSA ads for Rock the Vote, a non-profit organization in the United States geared toward increasing voter turnout in the United States Presidential Election among voters ages 18 to 24. That same year Kiedis appeared in a television special where he discussed his love for the ocean and raising awareness for ocean pollution. Since their beginning, the band has been very outspoken about the environment, supporting various environmental causes and including their views of the environment in lyrics.

On September 24, 1991, Blood Sugar Sex Magik was released. "Give It Away" was released as the first single; it eventually became one of the band's biggest and most well known songs, winning a Grammy Award in 1992 for "Best Hard Rock Performance With Vocal" and became the band's first number one single on the Modern Rock chart The ballad "Under the Bridge" was released as a second single, and went on to reach No. 2 on the Billboard Hot 100 chart, the highest the band has reached on that chart as of 2016, and became one of the band's most recognizable songs. Other singles such as "Breaking the Girl" and "Suck My Kiss" also charted well.

The album sold over 12 million copies. Blood Sugar Sex Magik was listed at number 310 on the Rolling Stone magazine list of The 500 Greatest Albums of All Time, and in 1992 it rose to No. 3 on the U.S. album charts, almost a year after its release. The band kicked off their Blood Sugar Sex Magik tour which featured Nirvana, Pearl Jam and Smashing Pumpkins, three of that era's biggest up and coming bands in alternative music, as opening acts.

In September 1992, the Peppers, with Marshall, performed "Give It Away" at the MTV Video Music Awards. The band was nominated for seven awards including Video of the Year (which they did not obtain); however, they did manage to win three other awards, including Viewer's Choice. On February 24, 1993, the band, along with George Clinton & the P.Funk All-Stars and Weapon of Choice, performed "Give It Away" at the Grammy Awards, a song which won the band their first Grammy later that evening. The performance marked the end of the Blood Sugar Sex Magik tour and Marshall's final performance with the band. The band had planned to begin a follow-up to Blood Sugar Sex Magik with Marshall. However, when it came time to play music, Marshall was always busy, so the band decided that Marshall failed to fit with their Future plans and he was dismissed.

When the band recorded One Hot Minute (1995) Kiedis had turned to drugs once again, which resulted in darker lyrics. He began to write about anguish, and the self mutilating thoughts he would experience as a result of his heroin and cocaine addiction. The album also featured tributes to close friends the band lost during the recording process including Kurt Cobain on the song "Tearjerker" and River Phoenix, on the song "Transcending".

The band was invited by the Beastie Boys and the Milarepa Fund to perform at the Tibetan Freedom Concert in June 1996 in San Francisco. They also performed at the June 1998 Washington DC concert as well. The concerts, which were held worldwide, were to support the cause of Tibetan independence.

After Navarro's departure in early 1998, Red Hot Chili Peppers were on the verge of breaking up. Flea told Kiedis, "the only way I could imagine carrying on [with Red Hot Chili Peppers] is if we got John back in the band." Kiedis was surprised and thought there was no way Frusciante would ever want to work with him as the two still had unresolved personal problems from when Frusciante quit in 1992. With Frusciante free of his addictions and ailments, Kiedis and Flea thought it was an appropriate time to invite him back. In April 1998, when Flea visited him at his home and asked him to rejoin the band, Frusciante began sobbing and said "nothing would make me happier in the world." Flea decided to contact Kiedis and have him meet with John to try and resolve any personal problems that the two might have had. Flea was relieved to find out that both had no bad blood towards each other and were once again excited to make music together. Within the week and, for the first time in six years, the reunited foursome jump-started the newly reunited Red Hot Chili Peppers. Anthony Kiedis said of the situation: "For me, that was the defining moment of what would become the next six years of our lives together. That was when I knew that this was the real deal, that the magic was about to happen again. Suddenly we could all hear, we could all Listen, and instead of being caught up in our finite little balls of bullshit, we could all become players in that great universal orchestra again."

After witnessing Frusciante's recovery from his heroin addiction, Kiedis wrote many songs inspired by rebirth and the meaning of life on Californication (1999). He was also intrigued by the life lessons, that the band had learned, including Kiedis' experience with meeting a young mother at the YMCA, who was attempting to battle her crack addiction while living with her infant daughter.

The writing and formation of the band's next album, By the Way began immediately following the culmination of Californication's world tour, in spring 2001. As with Californication, much of the creation took place in the band members' homes, and other locations of practice, such as a recording studio stage. Kiedis recalled of the situation: "We started finding some magic and some music and some riffs and some rhythms and some jams and some grooves, and we added to it and subtracted from it and pushed it around and put melodies to it." Frusciante and Kiedis would collaborate for days straight, discussing and sharing guitar progressions and lyrics. For Kiedis, "writing By the Way ... was a whole different experience from Californication. John was back to himself and brimming with confidence."

On By the Way (2002), Kiedis was lyrically influenced by love, his girlfriend, and the emotions expressed when one fell in love. Drugs also played an integral part in Kiedis' writings, as he had only been sober since December 2000. Tracks like "This Is the Place" and "Don't Forget Me" expressed his intense dislike for narcotics and the harmful physical and emotional effects they caused him. Stadium Arcadium (2006) continued the themes of love and romance; Kiedis stated, that "love and women, pregnancies and marriages, relationship struggles—those are real and profound influences on this record. And it's great, because it wasn't just me writing about the fact that I'm in love. It was everybody in the band. We were brimming with Energy based on falling in love." I'm With You (2011) again featured Kiedis writing about the loss of a close friend this time in the song "Brendan's Death Song", a tribute to club owner Brendan Mullen who gave the band some of their earliest shows and showed support to them throughout their career.

In November 2003, the Chili Peppers released their Greatest Hits album, which featured two new songs, "Fortune Faded" and "Save the Population". The two songs were selected out of sessions that generated fifteen tracks and Smith later said the band had hopes to use along with new compositions to create a full album after finishing the tour, but the idea was vetoed by Frusciante because his musical influences and styles had evolved and he wanted to do something new.

In October 2004, Kiedis released his autobiography Scar Tissue. It tells his life story from birth in 1962 until 2004. The book follows many major events for Kiedis such as growing up in Los Angeles, coming in contact with drugs at a young age, forming the band, and the troubling drug addictions he experienced during his career.

In September 2005, the band performed "Under the Bridge" at the ReAct Now: Music & Relief benefit which was held to raise money for the victims of Hurricane Katrina. The live event, which was broadcast on various television states, raised $30 million.

The record's first single, "Dani California", was the band's fastest-selling single, debuting on top of the Modern Rock chart in the U.S., peaking at No. 6 on the Billboard Hot 100, and reaching No. 2 in the UK. "Tell Me Baby", released next, also topped the charts in 2006. "Snow ((Hey Oh))" was released in late 2006, breaking multiple records by 2007. The song became their eleventh number one single, giving the band a cumulative total of 81 weeks at number one. It was also the first time three consecutive singles by the band made it to number one. "Desecration Smile" was released internationally in February 2007 and reached number 27 on the UK charts. "Hump de Bump" was planned to be the next single for the US, Canada, and Australia only, but due to positive feedback from the music video, it was released as a worldwide single in May 2007.

In July 2007, the band performed on behalf of former U.S. Vice President Al Gore who personally invited the band to perform at the London version of his Live Earth concerts which were held to raise awareness towards global warming and solving the most critical environmental issues of our time. Gore said on getting the band to perform "I was pushing and pushing them that no matter how difficult it was, that it was important."

In October 2008, Flea appeared in a Vote for Change ad voicing his support for Barack Obama for President of the United States in the upcoming election.

In May 2009, Kiedis was honored with the Stevie Ray Vaughan Award at the fifth annual MusiCares event for his dedication and support of the MusiCares MAP Fund and for his commitment to helping other addicts with the addiction and recovery process. Kiedis' fellow band members, minus Frusciante were on hand to pay tribute and under the name, 'The Insects', Kiedis, Smith, Flea along with Ron Wood, Josh Klinghoffer and Ivan Neville performed a brief set of cover songs.

The band officially began recording their tenth studio album with Producer Rick Rubin in September 2010. According to Rubin, the band recorded enough material to release a second double album, following Stadium Arcadium but ultimately decided not to. Rubin notes, "it was painful not to share all of the material that we had, but we felt it would be too much. We really wanted it to be twelve songs but it ended up being fourteen just because nobody could agree on which twelve." The recording process lasted until March 2011. Many of the songs were written between October 2009 and August 2010 and according to Flea around 60–70 songs were written in the ten months prior to entering the studio to record the album.

Current Guitarist Klinghoffer's style employs a wide range of his own unconventional guitar effects and vocal treatments. In his debut Chili Peppers album, I'm With You (2011), he focused heavily on producing a textured, emotional sound to complement the vocals and atmosphere of each song. He has stated that he is a huge fan of jazz and funk, which does express itself in many of the album's tracks.

The band performed a free concert in downtown Cleveland, Ohio on April 15, 2012 in support of President Obama's re-election campaign. The requirement for getting into the concert was agreeing to volunteer for the Obama 2012 phone bank. The event quickly met its capacity limit after being announced.

The band, especially Flea, has been very outspoken towards guns and gun violence sometimes speaking out about the issue during the band's concerts. In 2013, on his Twitter page, Flea posted "why anyone would ever want to own an automatic weapon I will never ever understand. it's a pathetic useless concept for sick people. Automatic, semi automatic, I don't care. I'm against em... Melt em all down turn em into sculptures there is no need for them on earth. in many countries the cops have no guns and they do perfectly fine. No civilians should be allowed to have guns. none. and i dont think the cops should have guns either. change the constitution."

Flea's electric bass style can be considered an amalgamation of funk, psychedelic, punk, and hard rock. The groove-heavy, low-tuned melodies, played through either finger-picking, or slapping, contributed to their signature style. While Flea's slap bass style was prominent in earlier albums, albums after Blood Sugar Sex Magik have more melodic and funk-driven bass lines. He has also used double stops on some newer songs. Flea's bass playing has changed considerably throughout the years. When he joined Fear, his technique centered largely around traditional punk rock bass lines, however he was to change this style, when Red Hot Chili Peppers formed. He began to incorporate a "slap" bass style, that drew influence largely from Bootsy Collins. Blood Sugar Sex Magik saw a notable shift in style as it featured none of his signature technique but rather styles, that focused more on traditional and melodic roots. His intellectual beliefs, on how to play the instrument, were also altered: "I was trying to play simply on Blood Sugar Sex Magik because I had been playing too much prior to that, so I thought, 'I've really got to chill out and play half as many notes'. When you play less, it's more exciting—there's more room for everything. If I do play something busy, it stands out, instead of the bass being a constant onslaught of notes. Space is good."

On October 17, 2015, Kiedis and Flea hosted the annual benefit for the Silverlake Conservatory of Music. The band performed a special rare acoustic set and John Legend headlined the event which also includes dinner and a silent auction. Only 300 tickets were available costing $2,500 each.

On April 29, 2016, Chad Smith and Will Ferrell hosted the Red Hot Benefit Comedy + Music Show & Quinceanera. The benefit featured a performance by the Chili Peppers along with comedy acts selected by Ferrell and Funny or Die. A portion of the proceeds went to Ferrell's Cancer for College and Smith's Silverlake Conservatory of Music. On February 12, 2018, Smith once again joined Ferrell at his One Classy Night benefit at the Moore Theater in Seattle to help raise money for Cancer for College. The event raised $300,000 in college scholarship money for students who have survived cancer, and has raised 2.3 Million to date.

In a December 2017 interview with ABC News, Drummer Chad Smith stated that "there's not gonna be any more touring" in 2018 (with the exception of three festival appearances in South America in March 2018), and that the Red Hot Chili Peppers will spend most of the year focusing on their twelfth studio album. He explained, "We're just gonna take a break for the rest of this year, and then we'll start up [and] probably write some more songs next year. Hopefully [we'll] make a record at some point. That's the plan."

On February 22, 2018, Flea wrote a passionate and revealing op-ed through Time magazine's website about the current Opioid crisis and his own personal history of drug addiction. Flea, who has been very private about his past addictions, revealed that he finally got clean in 1993 however after breaking his arm following his 2015 snowboarding accident the temptations were there due to the Oxycontin painkillers prescribed by his Doctor. "I’ve been around substance abuse since the day I was born. All the adults in my life regularly numbed themselves to ease their troubles, and alcohol or drugs were everywhere, always. I started smoking weed when I was eleven, and then proceeded to snort, shoot, pop, smoke, drop and dragon chase my way through my teens and twenties. Addiction is a cruel disease, and the medical community, together with the government, should offer help to all of those who need it."