After various modeling work, he made his acting debut as Leo du Pres on the ABC daytime soap opera All My Children and later starred as Danny McCoy on NBC's Las Vegas.

His mother, Bonnie L. (Bachmeier) Kemper, is a retired teacher and local businesswoman, and his father, Larry Duhamel, is an advertising salesman.

[12] Duhamel began his acting career as an extra in the music videos for Donna Summer's "I Will Go With You (Con te partirò)" and Christina Aguilera's "Genie in a Bottle" in 1999.

His work on the show, especially his character's pairing with Greenlee Smythe (portrayed by actress Rebecca Budig), garnered critical acclaim.

In 2003, Duhamel landed a primetime role on the NBC show Las Vegas, playing the head of security for the Montecito Casino, Danny McCoy.

Duhamel made his big-screen acting debut in 2004's Win a Date with Tad Hamilton!, then starred in the thriller Turistas (2006).

In 2014 Duhamel starred in the touching drama You're Not You (2014) playing the husband of Kate (Hilary Swank), who has the degenerative disease ALS.

On March 23, 2013, Duhamel hosted the 2013 Kids' Choice Awards, which was broadcast live from Los Angeles, California.

[22] On February 11, 2019, it was announced that Duhamel had been cast as Sheldon Sampson in the Netflix superhero series, Jupiter's Legacy.

[24] In February 2021, it was announced that Duhamel would co-star opposite Jennifer Lopez in the upcoming film Shotgun Wedding, replacing Armie Hammer, who had left the project in January, following controversy concerning sexually explicit social media activity.

[26] In early 2022, it was announced that Duhamel had been cast as a series regular on The Mighty Ducks: Game Changers, for its second season, as Colin Cole, a former NHL player-turned-coach who runs the hockey institute.

[29][30] Duhamel is a spokesman for North Dakota tourism and has appeared in promotional videos for the state over the past decade.

[48] On April 8, 2016, Duhamel posted a selfie in which he wore a T-shirt bearing the name of Doug Burgum, then a candidate for the Republican nomination for governor of North Dakota in the 2016 election.

[49] On June 28, 2023, Duhamel endorsed Burgum, then governor of North Dakota, in the 2024 Republican Party presidential primary.

[52] In October 2023, in an interview on In Depth with Graham Bensinger, Duhamel said: "And the older I got, the more I wanted to come back here [to North Dakota].