He began his career as a child actor and achieved a breakthrough with his role as Landry Clarke in the NBC drama series Friday Night Lights (2006–2011).

Plemons has acted in supporting roles in film such as The Master (2012), Bridge of Spies (2015), Game Night (2018), The Irishman (2019), Judas and the Black Messiah (2021) and Killers of the Flower Moon (2023).

[3] He is the younger of two children to Jim Bob, a firefighter and amateur rodeo competitor, and Lisa (Cason) Plemons, a special education trainer.

[11] He later appeared in Like Mike (2002) and When Zachary Beaver Came to Town (2003), with guest roles on the television series Judging Amy, The Lyon's Den, CSI: Crime Scene Investigation, and Grey's Anatomy between 2003 and 2006.

[13] When hit by co-star Taylor Kitsch (playing Tim Riggins) Plemons' chin split open, requiring eleven stitches.

In 2012, Plemons also had a supporting role in the Paul Thomas Anderson drama The Master as the son of Philip Seymour Hoffman's character, an actor to whom his physical appearance has been compared.

Plemons played mobster Kevin Weeks in the Boston-set mob film Black Mass, starring Johnny Depp, which opened in theaters in September 2015.

In 2017, he appeared in the Doug Liman thriller film American Made, the Scott Cooper western Hostiles, and Steven Spielberg's historical drama The Post.

Plemons played Robert Daly, the episode's main character and a sadistic introvert, and was nominated for the Primetime Emmy Award for Outstanding Lead Actor in a Limited Series or Movie.

In 2018, Plemons had supporting roles in two films, the comedy Game Night and Adam McKay's Dick Cheney biopic Vice, which he narrated.

In 2020, Plemons received critical praise and a Gotham Independent Film Award nomination for Best Actor for his lead performance in Charlie Kaufman's psychological drama I'm Thinking of Ending Things.

[32] In the same year, Plemons starred in the supernatural horror film Antlers, again collaborating with director Scott Cooper,[33] and starred once again alongside his real life partner and Fargo co-star Kirsten Dunst in Jane Campion's western drama The Power of the Dog,[34] for which he has received praise and a number of accolades, including a nomination for the Academy Award for Best Supporting Actor.