Groening was born on February 15, 1954 in Portland, Oregon USA. He grew up in Portland, and attended Ainsworth Elementary School, and Lincoln High School. He was the middle child of five children. His Norwegian mother, Margaret Wiggum, was once a teacher, and his German father, Homer Philip Groening, was a filmmaker, advertiser, writer and cartoonist. Homer, born in Main Centre, Saskatchewan, Canada, grew up in a Mennonite, Plautdietsch-speaking family. Matt's grandfather Abram Groening was a professor at Tabor College, a Mennonite Brethren liberal arts college in Hillsboro, Kansas before moving to Albany College (now known as Lewis and Clark College) in Oregon in 1930.
From 1972 to 1977, Groening attended The Evergreen State College in Olympia, Washington, a liberal school which he described as "a hippie college, with no grades or required classes, that drew every weirdo in the Northwest." He served as the editor of the campus newspaper, The Cooper Point Journal, for which he also wrote articles and drew cartoons. He befriended fellow cartoonist Lynda Barry after discovering that she had written a fan letter to Joseph Heller, one of Groening's favorite authors, and had gotten a reply back. Groening has credited Barry with being "probably biggest inspiration." He has also cited the Disney animated film One Hundred and One Dalmatians as what got him interested in cartoons.
Groening and Deborah Caplan married in 1986 and had two sons together, Homer (who goes by Will) and Abe, both of whom Groening occasionally portrays as rabbits in Life in Hell. The couple divorced in 1999 after thirteen years of marriage. Following this, Groening was in a six-year relationship with dating expert Lauren Frances.
Regarding his ethnic background, Groening has humorously remarked, "My background is Norwegian and German, two of the unfunniest ethnic groups in the history of the world."
Groening identifies himself as agnostic and a liberal and has often made campaign contributions to Democratic Party candidates. His first cousin, Laurie Monnes Anderson, is a member of the Oregon State Senate representing eastern Multnomah County.