Huisman's music career began as the singer and guitarist for the Dutch band Fontane, which released singles and was featured on movie soundtracks in the early 2000s.

Huisman played Sonny in HBO's Treme and replaced Ed Skrein as Daario Naharis in Game of Thrones, joining as a series regular.

His filmography includes roles in films such as Wild (2014), The Ottoman Lieutenant (2017), The Guernsey Literary and Potato Peel Pie Society (2018), and the Discovery Channel's miniseries Harley and the Davidsons.

[11] In 2006, Huisman made his first foray into the international acting world with a supporting role in an episode of the British TV series Dalziel and Pascoe.

He followed this with a role as Ernest II, Duke of Saxe-Coburg and Gotha in The Young Victoria, and the BBC made-for-TV drama Margot in which he portrayed Rudolf Nureyev.

[12] During his time on Treme, Huisman also played a small supporting role in the apocalyptic action film World War Z and started recurring as Liam McGuinnis on Nashville.

Huisman replaced English actor Ed Skrein in the role of Daario Naharis for the fourth season (2014) of Game of Thrones.

[15] In 2014, Huisman appeared in the Academy Award-nominated biographical drama film Wild[16] and starred in the advertising campaign for Chanel No.5's The One That I Want, which was directed by Baz Luhrmann.

[26] The film co-starred Gugu Mbatha-Raw as his childhood sweetheart, and later fiancée, who is diagnosed with terminal cancer, and Steve Coogan and Christopher Walken also appear.

Also in 2018, Huisman starred opposite Lily James as Dawsey Adams, the male lead in the romantic drama The Guernsey Literary and Potato Peel Pie Society, based on the 2008 novel of the same name.

Huisman plays Steven Crain, the oldest sibling, who becomes a published writer of supernatural books, including a memoir about his family's time living at Hill House.