He is known for his roles in films such as Monsters (2010), Argo, Killing Them Softly (both 2012), Batman v Superman: Dawn of Justice (2016), Speak No Evil, and Nightbitch (both 2024).

[8] In 2001, he appeared in Wrong Numbers, written and directed by Alex Holdridge, which won the Audience Award at the Austin Film Festival.

2010 saw the release of the alien invader film Monsters by Gareth Edwards, in which McNairy starred and featured largely improvised dialogue and was shot in Mexico, Guatemala, Costa Rica, and Texas.

[14] This led to a string of high-profile roles, including Ben Affleck's Argo,[2] Gus Van Sant's Promised Land, and Lynn Shelton's Touchy Feely opposite Rosemarie DeWitt.

McNairy filmed his second movie with Michael Fassbender, Leonard Abrahamson's Frank, and co-starred in Jaume Collet-Serra's Non-Stop, opposite Liam Neeson and Julianne Moore.

[22] McNairy next appeared in Taurus, alongside Machine Gun Kelly (who also co-wrote the script) and Megan Fox, which premiered at the 72nd Berlin International Film Festival.

[23] He also reunited with Andrew Dominik in the 2022 film Blonde, an adaptation of Joyce Carol Oates's historical fiction novel that chronicles the inner life of Marilyn Monroe.

[25] McNairy portrayed folk singer-songwriter Woody Guthrie in the 2024 Bob Dylan biopic A Complete Unknown, which starred Timothée Chalamet.

In February 2022, it was announced that McNairy would star alongside Michael Shannon, Emilia Clarke and Dane DeHaan in an upcoming Joseph McCarthy biopic.

[29] That same month, McNairy was announced as part of the cast for Blood for Dust, an action thriller, also including Kit Harington and Josh Lucas.

[32][33] He has worked on a number of other projects as an actor and producer, including 2012's A Night in the Woods; and Angry White Man, Dragon Day, and The Off Hours, all released in 2011.