For playing identical twins in Paul Thomas Anderson's period drama There Will Be Blood (2007), he was nominated for the BAFTA Award for Best Supporting Actor.

For his portrayal of Beach Boys founder Brian Wilson in Love & Mercy (2014), he earned a Golden Globe nomination for Best Supporting Actor.

In 2018, he starred as a convicted murderer in the Showtime miniseries Escape at Dannemora, for which he received a Primetime Emmy Award nomination for Outstanding Supporting Actor.

[5] Dano continued his education at Wilton High School, graduating in 2002, and attended Eugene Lang College in New York City.

[8] Dano made his Broadway debut at age twelve in John Tillinger's revival of Inherit the Wind, alongside George C. Scott and Charles Durning.

Dano acted in his first major film role when he was sixteen, playing Howie Blitzer, a teenage boy who becomes involved with a middle-aged ephebophile (Brian Cox) in L.I.E.

He came to greater attention in 2006, when he played Dwayne, a voluntarily mute teenager as part of an ensemble in the comedic drama Little Miss Sunshine, which received critical acclaim and collective awards for its cast.

"[11] Peter Travers remarked, "All praise to the baby-faced Dano...for bringing sly cunning and unexpected ferocity to Plainview's most formidable opponent.

"[12] Rolling Stone magazine included Dano in its Hot List for 2007, calling his performance style "Daniel Day-Lewis + Billy Crudup × Johnny Depp.

"[13] Dano appeared in several additional Broadway productions, including A Thousand Clowns at the Roundabout Theatre, and in Ethan Hawke’s directorial debut, Things We Want, during its 2007 Off-Broadway run.

[14] In Fall 2016, he appeared in a video as an onstage "stand-in" during the Nostalgic for the Present concert tour of Australian singer Sia, for her song "Bird Set Free.

[18] The film has earned a 94% on Rotten Tomatoes with the consensus reading, "Wildlife's portrait of a family in crisis is beautifully composed by director Paul Dano -- and brought brilliantly to life by a career-best performance from Carey Mulligan".

[25][26] The film was released in 2022 to universal acclaim;[27] with Dano's performance earning praise from Pete Hammond of Deadline Hollywood describing him as "terrific as the genuinely nice and loving father torn between following his own career and caring for his wife and family under increasingly difficult circumstances" and Stephanie Zacharek of Time including Dano in Time's Top 10 movie performances of 2022 describing his portrayal as "the sum of all the things that so many men of that generation just didn't know how to be; we also see a deep well of love, no less real for being left unexpressed.

[29] In March 2022, it was announced that Dano would make his comic debut writing The Riddler: Year One for DC's Black Label imprint.

[30] In September 2022, it was announced that Dano would star in Craig Gillespie's Dumb Money, an adaptation of Ben Mezrich's The Antisocial Network, alongside Seth Rogen, Sebastian Stan and Pete Davidson.

[36] The same year, Dano appeared in the television series Mr. & Mrs. Smith with Donald Glover, Maya Erskine, Michaela Coel and John Turturro.