Following Tom DeLonge's second departure from Blink-182 in early 2015, Skiba was brought on to fill in for three shows and was later made a full-time member.

His mother, Joan Skiba, is a fourth and fifth grade teacher at Woods Creek Elementary School in Crystal Lake, Illinois.

[5][3] Skiba studied design at Chicago's Columbia College but left in 1996 to form Alkaline Trio with drummer Glenn Porter and bassist Rob Doran.

The band released their debut full-length Goddamnit on Asian Man Records in 1998, followed by Maybe I'll Catch Fire and the compilation Alkaline Trio in 2000.

Good Mourning followed in 2003, marking the band's first album with drummer Derek Grant, formerly of Suicide Machines and Thoughts of Ionesco.

Following a five-year hiatus from the studio and a second throat surgery for Skiba,[6][7] the band released their ninth album, Is This Thing Cursed?, on August 31, 2018.

Following the departure of Tom DeLonge from Blink-182 in 2015, Mark Hoppus announced that Skiba would "fill in" for the band and performed two club shows and a slot at the Musink festival in March 2015.

[11] On February 13th 2025, Skiba joined his former band on stage to peform "Bored to Death" alongside Tom DeLonge during a benefit show in the Los Angeles' Hollywood Palladium to help Los Angeles wildfire relief efforts with Alkaline Trio as supporting act.

[14] Also in 2006, Skiba contributed to the track "Rock 'n' Roll High School" featured on Brats on the Beat: Ramones for Kids, a tribute album released on Go-Kart Records.

On August 18, 2009, at Debonair Social Club in Chicago, Skiba, Grant and Greg Corner and Jonny Radtke of Kill Hannah debuted the supergroup cover band Them Crooked Vulvas (and occasionally played under the name A Perfect Circus).

[15][16] In January 2012, Skiba released an EP along with former Angels and Airwaves and The Offspring drummer Atom Willard under the moniker The Hell.

[18] In early 2013, Matt Skiba encouraged Mike Park of Asian Man Records to release The Smith Street Band's first two albums in America.

[20] Although he started out as an avid player of Gibson Les Pauls, Skiba currently plays Fender Jaguar HH's.

Along with his own amps, the profiled sounds that were used include: Skiba is a vegan and practices Transcendental Meditation according to an interview with AOL Interface.

He said that the clear and calm state of mind it provides has greatly helped his creative process, though initially he believed the "tortured soul" mindset was more beneficial.

The book Catching the Big Fish by David Lynch caused him to change his mind and he now believes a calm state is more artistically helpful.

[26][27][28] Matt purchased a membership in the Church of Satan organization back in the early days of Alkaline Trio, saying, "to me Anton LaVey was...very punk rock".