DeLonge was born in Poway, California, on December 13, 1975. His father, Thomas DeLonge Sr., was an oil company executive, and his mother, Connie, a mortgage broker. His first musical instrument was a trumpet, which he received as a Christmas gift at age 11. Despite his early interest in music, becoming a musician was not his first calling. DeLonge originally planned to become a firefighter, and participated in the San Diego Cadet Program. He first picked up the guitar from a friend at church camp, and became preoccupied by the instrument. DeLonge received his first guitar as a Christmas present from two friends in the sixth grade – "a beat-up, shitty acoustic guitar that was worth about $30." He gathered his brother, Shon, and sister, Kari, as an audience for his original songs.

DeLonge grew to prominence playing pop punk music. Southern California had a large punk population in the early 1990s, aided by an avid surfing, skating and snowboarding scene. In contrast to East Coast punk music, the West Coast wave of groups, Blink included, typically introduced more melodic aspects to their music. "New York is gloomy, dark and cold. It makes different music. The Californian middle-class suburbs have nothing to be that bummed about," said DeLonge. In a 2011 article, he outlined six musical acts that impacted his growth as a musician, among them Stiff Little Fingers, U2, Depeche Mode, New Order, Fugazi, and the Descendents. The latter was his main influence when he began playing guitar; early recordings such as Buddha were an attempt to emulate their sound. Following the Descendents, DeLonge once cited Screeching Weasel as the second biggest influence on his songwriting in his early career.

DeLonge formed his first successful band, Blink-182, in 1992. He was removed from Poway High School in the second half of his junior year for going to a basketball game while inebriated. He was forced to attend a different school for one semester, nearby Rancho Bernardo High School, where he became friends with Kerry Key, and his girlfriend Anne Hoppus. Rancho Bernardo organized Battle of the Bands competitions, and DeLonge signed up, performing an original song titled "Who's Gonna Shave Your Back Tonight?" to a packed auditorium. Drummer Scott Raynor was at the competition with his own group, which soon dissolved, after which he was introduced by friend Paul Scott to DeLonge at a party. The two began to organize jam sessions at Raynor's home, shifting through various bassists. The following summer, DeLonge's Desire to be in a legitimate band increased significantly – Hoppus characterized his passion as "incessant whining and complaining." Her brother, Bassist Mark Hoppus, was new to San Diego and she introduced the two one night that August. The two would jam for hours in DeLonge's garage, exchanging lyrics and writing new songs.

The band toured constantly between 1995–96, performing nationwide, as well as in Canada and in Australia. By March 1996, the trio began to accumulate a genuine buzz among major labels, resulting in a bidding war between Interscope, MCA and Epitaph. MCA promised the group complete artistic freedom and eventually signed the band, but Raynor held a great affinity for Epitaph and began to feel half-invested in the band when they passed over the label. Their second effort, Dude Ranch, hit stores the following summer and the band headed out on their first Warped Tour. When lead single "Dammit" began rotation at Los Angeles-based KROQ-FM, other stations took notice and the single was added to rock radio playlists across the country. Dude Ranch shipped gold by 1998, but the exhaustive touring schedule brought tensions among the trio. Raynor had been drinking heavily to offset personal issues, and he was fired by DeLonge and Hoppus in mid-1998 despite agreeing to attend rehab and quit drinking. Travis Barker, Drummer for tourmate The Aquabats, filled in for Raynor, learning the 20-song setlist in 45 minutes before the first show. Barker joined the band full-time in summer 1998 and the band entered the studio with Producer Jerry Finn later that year to begin work on their third album.

Following high school, DeLonge would work in construction, driving around a Diesel truck and handling concrete and piping. "I hated, hated, hated my job. You know those people who hate their job? That was me," he later said. He promptly quit when Blink-182 signed to MCA Records in 1996.

DeLonge was unsure if the band's status in the music industry would grow or last, and he expanded into Business beginning in 1998. He started a holding group, Really Likable People (RLP), with a US$20,000 investment. Following this, he co-founded Loserkids.com, a website specializing in youth-branded apparel.

DeLonge's early guitar tone was described as "clean to crisply overdriven." During those years, he tended to use Fender Custom Shop Stratocasters (and still occasionally uses in studio recordings), and his own Fender Tom DeLonge Statocaster, with Seymour Duncan Invader pickups, Ernie Ball strings, Dunlop tortex picks, and a Whirlwind Selector A/B/Y box. The Mesa/Boogie Triple Rectifier was key to DeLonge's early sound; he employed them to create a distorted sound. "A Mesa/Boogie is like a nuke: you plug it in and it fills up every piece of the sonic spectrum," he said. As his sound gradually grew cleaner, he grew away from the Mesa/Boogies. DeLonge employed the Marshall JCM900 amps for his work on Dude Ranch, in which he improved his guitar tone. In a September 1999 Guitar Player article, DeLonge outlined his intentions: "I'm the kind of Guitarist that wants the biggest, fattest, loudest, sound he can get." As such, he refrained from toying with his guitar equipment for several years. "I was just into punk-rock. I thought we were cooler than every other band. I thought punk was way cooler and we knew something other people didn’t know. Now I look and think, 'Fuck, there was a lot I didn't know!'" he later remarked.

In 1996, DeLonge began dating Jennifer Jenkins, with whom he had been friends since high school. They were married on May 26, 2001 at Coronado, California on San Diego Bay. The band Jimmy Eat World performed at the reception. DeLonge gave each of the groomsmen, including Mark Hoppus, silver yo-yos from Tiffany & Co. They live with their dogs in Del Mar, California, and have two children: a daughter (born 2002) and a son (born 2006).

With time off from touring, DeLonge felt an "itch to do something where he didn't feel locked in to what Blink was," and channeled his chronic back pain (a herniated disc) and resulting frustration into Box Car Racer (2002), a post-hardcore disc that further explores his Fugazi and Refused inspiration. Refraining from paying for a studio Drummer, he invited Barker to record drums on the project and Hoppus felt betrayed. The event caused great division within the trio for some time and an unresolved tension at the forefront of the band's later hiatus. Blink-182 regrouped in 2003 to record their fifth studio album, infusing experimentalist elements into their usual pop punk sound, inspired by lifestyle changes (the band members all became fathers before the album was released) and side projects. Blink's eponymous fifth studio album was released in the fall of 2003 through Geffen Records, which absorbed sister label MCA earlier that year. Critics generally complimented the new, more "mature" direction taken for the release and lead singles "Feeling This" and "I Miss You" charted high, with the latter becoming the group's second number one hit on the Billboard Modern Rock Tracks chart. Fans were split by the new direction, and tensions within the band—stemming from the grueling schedule and DeLonge's Desire to spend more time with his family—started to become evident.

In 2003, Gibson released his signature model, the Tom DeLonge Signature ES-333, which has only been available since its release in Brown and Cream, with a Natural neck and headstock. Along with his Gibson signature, Tom also used a baritone Fender Jazzmaster with a Seymour Duncan Invader live, as seen in AOL live sessions with the song "Obvious". The Tom DeLonge Signature starts with Gibson's classic semi-hollow body design and then extends it into punk rock with an overwound 'Dirty Fingers' humbucking pickup. Its thick, distorted tone is the Delonge's signature guitar tone and widely recognized as the quintessential Blink sound.

DeLonge first approached filmmaking when he directed the music video for the song "This Photograph is Proof (I Know You Know)" by Taking Back Sunday in 2004. He was fascinated by the medium, calling the process "so artistically satisfying," and he has since worked in film on Angels & Airwaves-related projects. In 2014, he co-directed the animated short film Poet Anderson: The Dream Walker.

In September 2005, after spending months avoiding publicity, DeLonge announced his new Angels & Airwaves project and promised "the greatest rock and roll revolution for this generation." His statements—containing predictions that the album would usher in an "entire new culture of the youth" and lead to the band's dominance—were regarded as highly grandiose in the press and mocked. Thoroughly utilized by the band, DeLonge often discussed minor details and plans for accompanying films and other promotional matter, and his managers approached him having an "intervention" in which they disquietingly questioned his frame of mind. His ambitious beliefs were intensified by his addiction to Vicodin, a drug which he used due to his back Problem and did not try out again when he was unable to obtain it for a week, hallucinating and deep in withdrawal. We Don't Need to Whisper, the band's debut studio album, was released in 2006, and their second, I-Empire, followed in 2007.

The Technology and design firm Modlife was then founded by DeLonge in 2007, around the time that Blink-182 decided to part ways. DeLonge explained in 2014 that he was pondering a "plan B," whereby musical acts could monetize other aspects of their creative portfolio—posters, books, VIP tickets, limited-edition releases—given the challenges of contracts offered by major music companies and the emergence of file-sharing. Modlife handles the official websites and fan clubs for a range of artists, including the White Stripes, Pearl Jam, and Kanye West.

DeLonge would reunite with Blink-182 near the end of 2008. Barker had been involved in a fatal private plane crash, which laid grounds for the band's reformation. DeLonge found out via the TV news at an airport while waiting to board a flight; within minutes, he was crying in his seat. "I thought he was going to die," says DeLonge, who quickly reached out to his former bandmate, mailing him a letter and photograph. "Instantly after the plane crash, I was like, 'Hey, I want to play music with him again.'" DeLonge was the first to approach the subject of reuniting, and Blink-182 announced their reunion, a new album, and a reunion tour in February 2009 at the 51st Annual Grammy Awards. Blink-182 embarked on a reunion tour of North America from July to October 2009, supported by Weezer and Fall Out Boy. The tour was wildly successful, selling out amphitheaters nationwide: "I was completely blown away and dumbfounded by how big that reunion tour was. [...] We were very fortunate, very blessed," DeLonge later said. "And truthfully, that's why we continued, because we were so blown away. We were like, "Wow, we got to suck this up and start acting like adults because this is beautiful.'"

In 2011, DeLonge launched Strange Times, a Web site devoted to extraterrestrial life, paranormal activity, cryptozoology, and conspiracy theories. All of DeLonge's Business entities exist under the RLP moniker, with the exception of Atticus Clothing, which was sold in 2005.

In June 2012, DeLonge was working on two films: a feature-length Poet film and a film based on Strange Times.

In December 2013, DeLonge released a children's book, The Lonely Astronaut on Christmas Eve. The plot of the book is described by Alternative Press as a "rocketeer spending a cold Christmas alone on the moon who is visited by extraterrestrial life". DeLonge participated in a charity auction benefiting Rady Children’s Hospital Foundation allowing fans to bid on a package including the book.

In DeLonge's public response to Hoppus and Barker's claims about him not wanting to participate in a new Blink-182 album, he said the "60-page Blink contract" he was handed required that a new album be recorded within six months, and also included language that temporarily prohibited the release of other various projects that he was already under contract for. He said: "All of these other projects are being worked, exist in contract form—I can't just slam the brakes and drop years of development, partnerships and commitments at the snap of a finger. I told my manager that I will do Blink-182 as long as it was fun and worked with the other commitments in my life, including my family." Two months later, DeLonge shed some light on what his other projects entailed, claiming that he was working with "best selling authors" to co-write 15 novels with accompanying Soundtrack EPs. He also expected to release four albums in 2015—two Angels & Airwaves albums and two solo albums—three of which would include a companion novel.

In 2015, Tom Delonge founded To the Stars Academy of Arts and Sciences, a breakthrough scientific research, aerospace and media company incorporating Angels & Airwaves and a number of his books, including the Sekret Machines franchise. Reported partners include Jim Semivan (Vice President Operations), Hal Puthoff (Vice President Science & Technology), Steve Justice (Aerospace Division Director) Luis Elizondo (Director of Global Security & Special Programs), Chris Mellon (National Security Affairs Advisor), Garry Nolan (Genetics Technologies Consultant), Paul Rapp (Brain Function & Consciousness Consultant), Norm Kahn (National Security & Program Management Consultant), Colm Kelleher (Biotech Consultant) and Adele Gilpin (Biomedical Research & Attorney).

Chasing Shadows (Sekret Machines #1) was released in April 2016. The release was a collaboration between DeLonge and NY Times Best Selling Author A. J. Hartley. In October 2016, DeLonge will release his third novel, Strange Times: The Ghost In The Girl. This time DeLonge will collaborate with award-winning author Geoff Herbach and the novel will be based around the same characters from the graphic novel, Strange Times: The Curse of Superstition Mountain, that DeLonge published and authored in 2015.