Duchene wasted little time making an impression after the Colorado Avalanche selected him with the No. 3 pick in the 2009 NHL Draft.

In 2009-10, the Haliburton, Ontario, native with the nonstop motor made Colorado's roster out of his first training camp; he and then-teammate Ryan O'Reilly became the first 18-year-olds to skate with the Avalanche. Duchene had an assist in his NHL debut on Oct. 1, 2009 and led all rookies with 55 points in 81 games. His 24 goals tied John Tavares, the No. 1 pick in 2009 by the New York Islanders, for the most among rookies and ranked second on the Avalanche, who clinched a Stanley Cup Playoff berth thanks in part to Duchene's decisive shootout goal against the Vancouver Canucks on April 6, 2010.

Duchene had three assists in the Avalanche's six-game loss to the San Jose Sharks in the first round of the playoffs. His impressive 2009-10 season earned him a spot on the NHL All-Rookie Team, and he finished third in Calder Trophy voting.

In 2010-11, Duchene became the youngest player (20 years, 10 days) in Avalanche history to reach 100 points in his NHL career and appeared in the NHL All-Star Game for the first time. In that game he scored a goal and took the first penalty shot in All-Star history, though he was stopped by New York Rangers goalie Henrik Lundqvist.

Duchene's 27 goals and 67 points in 2010-11 made him the youngest player in franchise history to lead the team in scoring. He became the Avalanche's youngest single-season scoring leader (20 years, 84 days), surpassing franchise icon Joe Sakic.

A knee injury kept Duchene out of Colorado's first five playoff games in 2014. He returned for the final two games of the series against the Minnesota Wild and had three points, but the Avalanche lost in seven games.

Beyond scoring, Duchene's fast reaction time has allowed him to be one of the best in the NHL at winning face-offs. He's won more than half of his draws in every season since 2010-11.

Duchene played four more seasons with the Avalanche before he was traded to the Ottawa Senators on Nov. 5, 2017 as part of a three-team trade that also sent center Kyle Turris from the Senators to the Nashville Predators. He was on pace for his best season in 2018-19 with 58 points (27 goals, 31 assists) in 50 games for the Senators before being traded to the Columbus Blue Jackets on Feb. 22, 2019.

After helping the Blue Jackets win a playoff series for the first time in their history by sweeping the Tampa Bay Lightning in the Eastern Conference First Round before losing to the Boston Bruins, Duchene became a free agent and signed a seven-year contract with the Nashville Predators on July 1, 2019. He had a goal and an assist in Nashville's 2-1 win against the Minnesota Wild on Nov. 15, 2022, to pass 700 points in the NHL, becoming the second player from the 2009 NHL Draft Class to do so (John Tavares).

Duchene was placed on unconditional waivers by the Predators on June 30, 2023, for the purpose of buying out the final three seasons of his contract. He signed a one-year, $3 million contract with the Dallas Stars on July 1, 2023, another one-year deal July 1, 2024, and a four-year, $18 million contract to stay with the Stars on June 19, 2025, in lieu of becoming an unrestricted free agent, after leading Dallas with 82 points (30 goals, 52 assists) in 82 regular-season games. He had the secondary assist on Sam Steel's goal at 2:37 of the second period in the Stars' 4-1 win at the Washington Capitals on Jan. 7, 2026, to make him the second player taken in the 2009 draft to reach 900 points in the League.