He is best known for his role as Mac on the FX/FXX comedy series It's Always Sunny in Philadelphia (2005–present), a show he created and co-developed with Charlie Day and Glenn Howerton and on which he continues to serve as an executive producer and writer.

He is also known for playing Ian Grimm on the Apple TV+ comedy series Mythic Quest (2020–present), which he co-created with Day and Megan Ganz as executive producers.

He later had more substantial parts in the films Latter Days and The Tollbooth, and a guest role in the Law & Order episode "Thrill".

When he was 21, a screenplay he wrote was optioned with Paul Schrader attached to direct, but the project fell through after a year of edits and rewrites.

[8] When he was 27 years old, he was waiting tables between acting jobs and had met Glenn Howerton through his agent, as well as meeting Charlie Day while shooting a horror film in New York City.

[9] After receiving offers from many of the networks, McElhenney chose to sign with FX as they allowed him more creative freedom, and the show was eventually titled It's Always Sunny in Philadelphia.

[8] McElhenney has said that 50 weeks per year are taken up by acting, producing, and writing for It's Always Sunny, though he did find time to appear in the Lost episode "Not in Portland".

[12] In 2017, McElhenney appeared in a guest role as a police officer in the acclaimed Fargo episode "The Law of Non-Contradiction".

[13][14] In 2020, McElhenney co-created the Apple TV+ comedy series Mythic Quest alongside Charlie Day and Megan Ganz.

In 2009, McElhenney and his wife Kaitlin Olson along with others purchased Skinner's Bar, now Mac's Tavern at 226 Market St in Philadelphia.

[27][28] On June 26, 2023, it was announced that both Ryan Reynolds and McElhenney were part of an investor group that bought a 24% equity stake in the Alpine F1 Team.

[29] McElhenney hired actress Kaitlin Olson to play Dee Reynolds on It's Always Sunny in Philadelphia, and became romantically interested in her "around season 2" of the series.

His co-star Charlie Day described the weight gain as "disgusting" and said that the rest of the cast was "a little on the fence about it for his own personal health and safety".