[3] Nyquist left the Black Bears after his junior year, signing a two-year, entry-level contract with the Detroit Red Wings, the team that drafted him 121st overall in 2008, on 25 March 2011.

[citation needed] Nyquist made his NHL debut with Detroit on 1 November 2011, in a 2–1 overtime loss to the Minnesota Wild.

[citation needed] He was recalled from Grand Rapids after forward Darren Helm suffered a deep gash to his right forearm in Game 1, when he was cut by the skate blade of Alexander Radulov, leading to season-ending surgery.

In addition to his NHL contributions in 2012–13, Nyquist was also the leading scorer for the Grand Rapids Griffins, recording 23 goals and 37 assists in 60 regular season games.

[9] On 20 August 2013, prior to the beginning of the 2013–14 season, the Red Wings signed Nyquist to a two-year, $1.9 million contract extension.

He finished the month with the second-most goals, 12, and was tied for fifth with 18 points to help the Red Wings post a 7–6–2 record and move into the first wild card spot in the Eastern Conference.

The Red Wings made him a qualifying offer to retain his NHL rights and on 5 July 2015, Nyquist filed for salary arbitration.

On 1 July 2019, Nyquist left the Sharks as a free agent and signed a four-year, $22 million contract with the Columbus Blue Jackets.

On 4 November 2020, it was announced that Nyquist underwent surgery on his left shoulder to address a labral tear and would miss 5-6 months.

As a free agent from the Wild, Nyquist opted to remain in the Central Division by agreeing to a two-year, $6.37 million contract with the Nashville Predators on 1 July 2023.

[24] Nyquist was selected as a replacement for Red Wings' teammate Johan Franzén to represent Sweden at the 2014 Winter Olympics, where he won a silver medal.

[26] Nyquist represented Sweden at the 2018 IIHF World Championship, where he recorded four goals and one assist in nine games, and won a gold medal.