In 2022, Centineo played Atom Smasher in the superhero film Black Adam and began starring in the Netflix spy-adventure series The Recruit.

[7] In the same year, he was cast as Ben Eastman in the Disney Channel comedy pilot Growing Up and Down, which was not picked up to series.

In 2019, he played the lead role of Brooks Rattigan in another Netflix romantic comedy film, The Perfect Date, which was released in April.

[23][24] Centineo appeared in the DCEU movie Black Adam playing Albert Rothstein / Atom Smasher.

In April 2024, it was announced that Centineo had joined the cast of Warfare, an A24 war movie written and directed by Alex Garland and Ray Mendoza.

[27] In 2019, Centineo co-founded Favored Nations[28][29] with his friend Josh Heller, a Los Angeles–based actor and lifestyle photographer.

[30] Centineo was inspired to found the nonprofit after teaming with Omaze for a contest that raised $280,000 for charity; the prize was a chance to go on a hike and have dinner with him.

[28] They are an intermediary between donors and charities; each donor can contribute to a charity from a list of nonprofit organizations that includes Black Lives Matter, Policing Equity, Know Your Rights Camp, Color of Change, The Bail Project, and the Florida Rights Restoration Coalition.

[39] In February 2020, Centineo revealed in an interview with Harper's Bazaar that from age 17 to 21, he had experienced "a really dark time in [his] life," during which he used alcohol and drugs.