Twenty seconds into the second period of Larkin's NHL debut for the Detroit Red Wings against the Toronto Maple Leafs on Oct. 9, 2015, the center from Waterford, Michigan, took a pass from Henrik Zetterberg and shot top shelf past goalie Jonathan Bernier. Larkin also added an assist in the 4-0 victory.

Selected in the first round (No. 15) of the 2014 NHL Draft, Larkin became the first teenager (19 years old) to play opening night since Mike Sillinger in 1990-91. He made the NHL after one season at the University of Michigan, where his 47 points (15 goals, 32 assists) led Big Ten rookies and placed him second in the NCAA among freshmen. Foregoing his final three years of college eligibility and signing a three-year entry-level contract, Larkin began his pro career with Grand Rapids in time for the American Hockey League playoffs, where he scored three goals and five points in six games.

In 2015-16, Larkin became the sixth rookie in Red Wings history to lead them in goals (23), the first since Mike Foligno scored 36 in 1979-80. He was also plus-11, scored five game-winning goals and took 221 shots on goal. Larkin became the first teenager since former Red Wings forward Steve Yzerman in 1984-85 to score goals in four consecutive games (Nov. 16-21 2015). He finished November with seven goals and 10 points in 13 games and was named NHL Rookie of the Month.

Invited to play at the 2016 Honda NHL All-Star Game, Larkin participated in the Fastest Skater competition during All-Star Weekend and had a time of 13.172 seconds, breaking Mike Gartner's record of 13.386 set the record in 1996, six months before Larkin was born.

At age 22, Larkin became the fifth-youngest player in Red Wings history to lead them in scoring with 63 points (16 goals, 47 assists) in 2017-18, behind Yzerman (18 years, 10 months in 1983-84), Mark Osborne (20 years and seven months in 1981-82), Marcel Dionne (20 years, seven months in 1971-72) and Dale McCourt (21 years, two months in 1977-78). He signed a five-year contract with Detroit on Aug. 10, 2018. On Jan. 13, 2021, Larkin was named the 37th captain in the history of the Red Wings, and first native of Detroit and born in Michigan.

Larkin signed an eight-year contract (average annual value of $8.7 million) with the Red Wings on March 1, 2023. He became the ninth player in team history with four consecutive 30-goal seasons in 2024-25 and the first to do it since Henrik Zetterberg from 2005-09. Larkin played all 82 games for the second time, finishing with 40 assists and 70 points.

Larkin opened the 2025-26 season with 11 points (five goals, six assists) in six games to become the third player in Red Wings history with multiple season-opening point streaks of at least six games (also accomplished in 2023-24), according to NHL Stats. He joined Steve Yzerman (seven games in 1988-89; six games in 1984-85) and Gordie Howe (six games in 1968-69 and 1961-62). He scored into an empty net to complete a 4-2 win against the Seattle Kraken in Detroit on Nov. 18, 2025, for his 600th NHL point.

Larkin won gold with Team USA at the Olympic Winter Games Milano Cortina 2026, the country's first in men's Olympic hockey since the 1980 Lake Placid Games.