Met with widespread critical acclaim, the Strokes' 2001 debut, Is This It, helped usher in the garage rock revival movement of the early-21st century—and ranks number eight on Rolling Stone's 100 Best Debut Albums of All Time, number two on Rolling Stone's 100 Best Albums of the '00s, 199 on Rolling Stone's 500 Greatest Albums of All Time and number four in the NME top 500 albums of all time.

The group began recording their follow-up in 2002 with Producer Nigel Godrich (best known for his work with Radiohead), but later split with him in favor of Gordon Raphael, the Producer of Is This It. Recordings with Godrich were never revealed. In August 2003, the band toured Japan, playing a couple of the upcoming songs: "Reptilia", "Meet Me In The Bathroom", "The Way It Is", "Between Love & Hate" (formerly known as "Ze Newie") and "12:51" (formerly known as "Supernova"). The band also played Paul Anka's "My Way" with Japanese lyrics. The Strokes released their second album Room on Fire in October 2003. It received praise from critics but was less commercially successful, although it still went gold. The album's sound maintained the Strokes' familiar reference points, while also evoking groups such as the Cars, Bob Marley, and Blondie. In the process, they made the cover of Spin Magazine for the second time, with each member receiving his own cover. They also made the cover of Rolling Stone for the first time. Additional media coverage of the band came from the relationship between Moretti and Actress Drew Barrymore, which ended in January 2007. The first single taken from Room on Fire was the song "12:51", which used distinct keyboard-like sounds produced by Valensi's guitar. The video was also directed by Roman Coppola, and was inspired by the Futuristic look of the 1980s film Tron. This consisted of a mainly black scene, with instances of glowing picton blue and riptide.

In November 2003, the Strokes played on Late Night with Conan O'Brien, performing "Reptilia", "What Ever Happened", "Under Control" and "I Can't Win". During the 2003/2004 "Room on Fire Tour", the band played with Kings of Leon as support act and Regina Spektor. While on tour, Spektor and the Strokes recorded the song "Modern Girls & Old Fashion Men", released as a B-side on the "Reptilia" single. Also during the tour, the band included the Clash's "Clampdown" as a cover, which was released as the B-side for "The End Has No End".

In late 2004, the Strokes revealed plans to release a live album. The Live in London LP was planned for release in October 2004, but was abandoned, reportedly due to recording quality problems. The chosen gig was one held at the legendary Alexandra Palace in North London.

In late September 2005, "Juicebox", the first single from the Strokes' then unreleased third album, was leaked online, forcing the single's release date to be advanced. The single was then released as an exclusive on online download services. "Juicebox" became the Strokes' second UK Top 10 hit, as well as their second US Modern Rock Top 10 success. During November and December 2005 the Strokes did a promotional tour for the still unreleased album, which involved doing one-off shows in major cities around the world. Their third album, First Impressions of Earth, was released in January 2006 to mixed reviews and debuted at number four in the US and number one in the UK, a first for the band. In Japan it went gold within the first week of release. It was also the most downloaded album for two weeks on iTunes. Fraiture claimed that the album was "like a scientific breakthrough". In January 2006, the band then made their second appearance on Saturday Night Live playing "Juicebox" and "You Only Live Once". The album was somewhat a departure from the band's two previous albums. One reason for this was a switch of producers from Gordon Raphael to David Kahne. Despite its initial strong sales, First Impressions of Earth received the worst reception, both commercially and critically, of all their albums.

In 2006, the band played 18 sold-out shows during their UK tour. In February 2006, the Strokes won "Best International Band" at the NME Awards. In March, the band returned to the US with their longest tour yet. The second single off First Impressions of Earth, "Heart in a Cage", was released in March 2006. During the summer of 2006, the Strokes played several festival dates in Europe, including the Hultsfred Festival in Sweden, Roskilde Festival in Denmark, the Oxegen Festival in Ireland, the Montreux Jazz Festival in Switzerland, the FIB (Festival Internacional de Benicàssim), Fuji Rock Festival and headlined the Pentaport Rock Festival in South Korea. They then toured Australia and Mexico in late August and early September, followed by the second leg of the United States tour. While in the US, the Strokes opened for Tom Petty & the Heartbreakers for five shows during their Highway Companion tour. The Strokes went on to complete another US tour. During this final tour Casablancas stated to fans that the band would be taking an extensive break after it finished. An e-mail was sent out soon afterwards by Strokes manager Ryan Gentles, confirming that "much needed break". A new band website went online in May 2007 along with the release of an alternate video to their single "You Only Live Once" directed by Warren Fu. The video also featured a brief interlude with "Ize of the World", also from First Impressions of Earth. The song "You Talk Way Too Much" was used in a commercial for the Ford Sync. Aleksandra Cisneros became the Strokes' new assistant manager in late 2007.

The Strokes frontman Julian Casablancas and Guitarist Nick Valensi started writing material for the album in January 2009, intent on entering the studio that February. Julian commented in Rolling Stone that they had completed about three songs that sounded like a mixture of 1970s rock and "music from the future". On March 31, 2009 from their MySpace account, the band announced the end of their "much needed hibernation period" and the commencement of new writing and rehearsing for a fourth full-length album, entitled Angles. This album would be different from the first three in that it would feature music written by the other four Strokes, rather than Casablancas writing ninety-five percent of the material again: "It's supercollaborative, and it sounds different," said Valensi, "but it has a Strokes vibe to it." In an NME article, Pharrell Williams expressed interest in producing this upcoming album. This followed the news that Casablancas had collaborated with Williams and Santigold on "My Drive Thru", a track commemorating the 100th anniversary of Converse's Chuck Taylor All-Stars shoe. The song was available as a free download from the official Converse site. The album was due to be released in late 2009, but disagreements about the songs' readiness forced the Strokes to scale back this date. On February 1, 2010, the Strokes announced on their website that the recording of the fourth album was being helmed by award-winning Producer Joe Chiccarelli. According to Chiccarelli in an interview with HitQuarters, the two camps first met in 2009 and, after finding they shared a similar mind space and similar thoughts on the potential direction of the new record, tried out some tracking. Not long after recording began, however, the band became frustrated with Chiccarelli's reserved production style. Only one song from these recording sessions, "Life Is Simple in the Moonlight", remained on the album's track listing. Inspired, in part, by bands like MGMT, Arctic Monkeys, and Crystal Castles, the Strokes decided to experiment with various production techniques, and recorded the rest of the album's material at Albert Hammond, Jr.'s home studio in upstate New York with award-winning Engineer Gus Oberg.

The Strokes confirmed that they would be headlining the Isle of Wight Festival, Lollapalooza, Roskilde Festival, Hurricane Festival, Splendour In The Grass, Rockness, Outside Lands Music and Arts Festival, On The Bright Side, and Austin City Limits Music Festival in 2010. Additionally, the Strokes were announced as the 2011 headliner for the Coachella Valley Music and Arts Festival and the New Orleans Jazz & Heritage Festival in May, Festival Internacional de Benicàssim, Oxegen, Paléo, Peace & Love and Super Bock Super Rock in July, and Reading Festival and Summer Sonic in August. They were also sub-headliners to Pulp at Leeds Festival during the bank holiday weekend in August. On June 9, 2010, at Dingwalls London, England, the band played a secret show under the name 'Venison' to a crowd of just 487. This was their first live gig since October 2006. The band did not play any new material.

The lead single from the new album, "Under Cover of Darkness", was released on February 9, 2011. The 7" was officially released on March 1, 2011 and contained another track from Angles, "You're So Right", as the B-side, followed by the album on March 18, 2011. "Taken for a Fool" was confirmed as the second single, which was sent to U.S. radio on May 24, 2011. On June 9, the Strokes announced that a music video for "Taken For a Fool" was in the works, and that it is directed by Laurent Briet. They revealed that the music video should be finished by the end of the month. The Strokes put out the music video for "Taken For a Fool" on July 8, 2011. In mid-March 2011, an interview with ShortList magazine revealed that the Strokes had already begun working on their fifth studio album. However, sessions were delayed due to the mixing process of Angles. Julian Casablancas and Nick Valensi both confirmed that there was material in the works as well as plenty of leftover material. Frontman Julian Casablancas claimed that the band was eager to begin working on new material and were already supposed to, but it took longer than expected to master Angles.

On December 5, 2013, Albert Hammond, Jr. said that he would be interested in playing solo as an opening act for the Strokes, if they announce another tour: "I would definitely ask the guys if I could open for them, that’d be amazing." In May 2014, the Strokes performed their first U.S. show in three years at the Capitol Theatre in Port Chester, NY, performing songs from Comedown Machine for the first time. The band played at three other shows in 2014, including two headlining slots at Governors Ball Music Festival in New York City and FYF Fest in Los Angeles. On November 12, 2014, it was announced the band would headline Primavera Sound in 2015 for the festival's 15th anniversary. On March 2, 2015, the band announced their second 2015 European festival headline appearance would be at London's annual British Summer Time: Hyde Park festival on June 18, 2015, the band's first London show in five years. The announcement takes the band's number of appearances slated for 2015 up to six, with them also playing Big Guava Music Festival in Tampa, Florida, Shaky Knees Festival in Atlanta, Georgia, Landmark Festival in Washington, DC and Austin City Limits in Austin, Texas as well as the previously announced, Primavera Sound 15th Anniversary. During their performance at Landmark Music Festival lead singer Julian Casablancas stated that the band is back in the studio working on a follow up to their 2013 album Comedown Machine. In late 2015, the Strokes announced another date; at Monterrey, Mexico, during the festivities of the newborn festival "Live Out".

After the release of Is This It, the band toured around the world—including Japan, Australia, New Zealand, Europe, and North America (the band opened for the Rolling Stones on numerous occasions during the North-American leg of their tour). The self-made mini-documentary "In Transit" was filmed during the summer tour of Europe. In August 2002, the band headlined UK's Carling Weekend festivals for the second time, subsequently playing at New York's Radio City Music Hall on a bill with the White Stripes. Jack White joined the Strokes on stage to perform the guitar solo on "New York City Cops". During that period, the band also appeared as musical guests on numerous late-night talk shows. Is This It yielded several singles and music videos, all of which were directed by Roman Coppola.

In October 2016 Guitarist Valensi indicated that the band were "slowly but surely working on an album, we’re kind of just in writing sessions". In July 2017 Albert Hammond said the Strokes are working with Rick Rubin. Albert Hammond Jr. took to Twitter to clarify that “we met and played a few music ideas for Rick to feel out a vibe but even a theoretical album plan would be years away, if at all.” He also tweeted, "Sorry everyone we are not in the studio recording" and that there were "a lot of unknowns and nothing worth speaking about at this time."

The band performed a series of festival dates taking place throughout early 2017. Festival dates include performances in Estéreo Picnic Festival as well as Lollapalooza Brasil, Lollapalooza Chile, and Lollapalooza Argentina. The band's first live performance of the year took place headlining the Estéreo Picnic Festival festival. The crowd in attendance of their Argentina show was reportedly a volume of 90,000 people. After the Lollapalooza Argentina show it was revealed that their headlining slot at the festival was, to this day, their "biggest show ever" by Fraiture on social media.

The band began rehearsing a fourteen-song set (an early blueprint of the Strokes’ 2001 debut, Is This It)—including, "Alone, Together," "Barely Legal," "Last Nite," "The Modern Age," "New York City Cops," "Soma," "Someday," "Take It or Leave It," and "This Life" (an early version of "Trying Your Luck"). Most of these songs now feature different lyrics. The band sent a demo to the newly reformed Rough Trade Records in the UK, sparking interest there, and leading to their first release (via the website of the UK magazine, NME, who gave away a free mp3 download of "Last Nite" a week prior to the physical release as part of The Modern Age EP in 2001). The EP sparked a bidding war among record labels, the largest for a rock band in years. In August 2001, the Strokes made their first appearance on the cover of the publication The Fader in its ninth issue.