The band formed in December of 1996, originally consisting of Skiba, Rob Doran (bass/vocals), and Glenn Porter (drums/vocals). 1997 saw the release of the band's first EP, Sundials. This was followed shortly after by the departure of Doran. He was replaced by Andriano, who had been the singer for Tuesday and bassist for the ska band Slapstick. The band released their second EP, entitled For Your Lungs Only, in 1998, which began to build them a sizable fan base in the American Midwest. Later that year, they released their first full-length album, Goddamnit, followed by Maybe I'll Catch Fire in 2000. Both were released on Asian Man Records. Also in 2000, the band released a collection of their previously-released EPs on a self-titled album.

Following the success of their Asian Man releases, Alkaline Trio signed to Vagrant. Joined by new drummer Mike Felumlee (previously of the Smoking Popes), From Here To Infirmary was released in 2001. It was their first album to see any interest from alternative radio and the mainstream media, with the semi-hit punk single "Stupid Kid" and the inclusion of the song "Armageddon" on the Tony Hawk's Underground video game. Their cover of "Over at the Frankenstein Place" was included in the compilation The Rocky Horror Punk Rock Show, an album made to pay tribute to the movie The Rocky Horror Picture Show.

After the release, Felumlee left the band too and was replaced by Grant, previously of The Suicide Machines.

Their next full-length album was Good Mourning, released in 2003, with the album's launch single "We've Had Enough" seeing a considerable amount of commercial success. The album was a significant departure from earlier works, featuring greater production value and a noticeable move toward a more mainstream sound.

The band has also appeared on various compilation albums, notably Plea for Peace Vol. 1 and Rock Against Bush Vol. 1. Skiba and Andriano have both independently recorded split records, Skiba with Kevin Seconds on Asian Man Records and Andriano with Mike Felumlee on Double Zero Records, as well as jointly performing backing vocal duties on the album This Is Unity music by Common Rider. They have also recorded two split EPs with bands who are no longer together: one with Hot Water Music in 2000 and the other with One Man Army in 2004.

Alkaline Trio released their fifth studio album on Vagrant Records, entitled Crimson, on May 24, 2005, which featured the single "Time to Waste." The single for this song also included bonus tracks produced by Mass Giorgini. The tracks "Mercy Me" and "Burn" have also been released as singles from the album.

In 2004 Andriano became a member of The Falcon, a super-group of consisting of The Lawrence Arms' bassist/co-vocalist Brendan Kelly (with who he had played with in Slapstick), and Neil Hennessy, drummer from The Lawrence Arms. The band released a 5-song EP in 2004, and its first full-length Unicornography in September of 2006.

In 2006 Matt Skiba collaborated with Josiah Steinbrick for the band Heavens.

In 2008 Alkaline Trio released Agony & Irony on Epic Records. The album charted at #13 on the Billboard 200.

Alkaline Trio's 7th studio album, This Addiction, is set for release on February 23rd 2010. This will be the first album under their own label, Heart & Skull, an offshoot of Epitaph.

Alkaline Trio is an American punk rock band that formed in McHenry, Illinois, in 1996. The band's line-up consists of Matt Skiba (vocals, guitar), Dan Andriano (vocals, bass), and Derek Grant (drums). To date, the band has released seven studio albums, including their newest, This Addiction, released on February 23, 2010.