Day attended Pennfield School and graduated from the Portsmouth Abbey School, both in Portsmouth, Rhode Island. He attended Merrimack College in North Andover, Massachusetts, majoring in art history in 1998. In May 2014, Day gave the commencement speech for Merrimack College’s graduating class and received an honorary Ph.D.

Day has been married to actress Mary Elizabeth Ellis since March 4, 2006. They met in 2001 and were dating in 2004 when they co-starred as incestuous siblings on Reno 911!. Ellis has a recurring role on It’s Always Sunny in Philadelphia as The Waitress, the object of the unrequited love and obsession for Day’s character. The couple had their first child, a son named Russell Wallace Day, in December 2011. They live in Los Angeles, California.

He starred in New Line Cinema’s Horrible Bosses in July 2011, with Jason Bateman, Jason Sudeikis, Kevin Spacey, Jennifer Aniston, Colin Farrell, and Jamie Foxx. He also had a role in the 2010 film Going the Distance, alongside Justin Long, Jason Sudeikis, and Drew Barrymore. In 2013, he voiced the character Art in the Pixar animated film Monsters University and appeared in Guillermo del Toro’s film Pacific Rim. In 2017, Day starred in Fist Fight, with Ice Cube. In it, Day plays Andy Campbell, a high school English teacher challenged by his co-worker, history teacher Ronald Strickland (Cube), to a fight after getting him fired. In 2018, he reprised his role for the Pacific Rim sequel, Pacific Rim: Uprising and had a role in Drew Pearce’s film Hotel Artemis, with Jodie Foster, Sterling K Brown, Brian Tyree Henry and Jenny Slate.

Day has also been a producer for the television shows How to Be a Gentleman and Unsupervised. Day hosted the November 5, 2011 episode of Saturday Night Live (SNL) with Maroon 5 as the musical guest. He was the second cast member from It’s Always Sunny in Philadelphia to host SNL (after Danny DeVito, though DeVito hosted SNL before It’s Always Sunny in Philadelphia premiered). DeVito made a special appearance during Day’s opening monologue. In September 2014, Day provided his voice for The Sims 4 TV spots.

A skilled musician, Day started to play the violin at the age of three. He can play the piano, accordion, trombone, guitar and harmonica, and has written and improvised some of the music featured in It’s Always Sunny in Philadelphia. In 2014, he received an honorary doctorate in performing arts from Merrimack College, where he also delivered that year’s keynote address.

He is the creator and producer of Fox comedy The Cool Kids, starring Vicki Lawrence, Martin Mull, David Alan Grier and Leslie Jordan and set in a retirement community. On August 9, 2019, Mythic Quest, a new half-hour comedy series written and produced by Day and Rob McElhenney, was announced as one of the original productions for Apple’s upcoming streaming service, Apple TV+.