The band began performing their own music, accompanied by a drum machine, and soon became fixtures on the Manhattan underground. Although they had a strong local following, they had a hard time getting a record deal. They did many live performances in New York but when Linnell broke his wrist in a biking accident and Flansburgh's apartment was broken into and all his guitars stolen, they set up the Dial-A-Song system with an answering machine hooked up to a tape of them playing popular songs. It soon caught the eye of Bar/None records and earned them a review in People magazine.
The duo released their self-titled debut album in 1986, and it became a college radio hit. The video for "Don't Let's Start" became a hit on VH1, earning them a broader following. In 1988 they released Lincoln. This album caused a major shock within the US music industry when in its first week of release it knocked U2's "The Joshua Tree" off the top of the Billboard College Charts (the US music industry's equivalent to the "Alternative/Independent" charts elsewhere in the world) after only a one week stay at the top (most were expecting U2 to be on top for the remainder of the year).
The first single from Lincoln, "Ana Ng" reached number 89 on the UK Billboard charts, and was No.1 in the College Charts, earning the attention of major labels. In 1990 they signed with Elektra Records, and released Flood. Flood earned them a gold album, thanks to the singles "Birdhouse in Your Soul", which reached number 6 in the UK charts, and "Istanbul (Not Constantinople)". Following those successes, Bar/None Records released the B-sides and rarities compilation Miscellaneous T in 1991.
The 1992 release of Apollo 18 saw Flansburgh and Linnell attract a supporting band, consisting of former Pere Ubu bassist Tony Maimone and drummer Brian Doherty. Several albums have followed, none quite as successful as Flood, but the decision to include their single "Boss of Me" as the theme song to the hit television series Malcolm in the Middle, as well as inclusion on the show's compilation CD, has brought a new audience to the band, largely thanks to the use of TMBG songs from all their previous albums (eg. the infamous punching-the-kid-in-the-wheelchair scene from the first MITM series was done to the strains of "Pencil Rain" from "Lincoln") "Boss of Me" became the band's second top-40 hit in the UK.
They Might Be Giants have also performed on other movie and television sound tracks, including The Oblongs, the ABC News miniseries Brave New World, and Ed and His Dead Mother. They also composed and performed the theme music for the Peabody Award-winning The Daily Show with Jon Stewart. More recently, they composed and performed the music for the MTV series Resident Life.
In 2001, a documentary about the band was made my AJ Schnack. Titled Gigantic: A Tale of Two Johns, the film won rave reviews, several awards, was featured in dozens of film festivals, and was released on DVD.
The band takes its name from a 1971 movie starring George C. Scott and Joanne Woodward (based on the play of the same name written by James Goldman.) In the film, George C. Scott plays Justin Playfair, a man who believes he is Sherlock Holmes; his psychiatrist (last name "Watson") goes along with him in search of Moriarty. Playfair defends Quixote's tilting at windmills, saying that the windmills of course were not giants, but thinking they might be shows imagination: "All the best minds used to think the world was flat. But what if it isn't? It might be round. And bread mold might be medicine. If we never looked at things and thought of what might be, why we'd all still be out there in the tall grass with the apes."