Duchesne signed as a free agent with the Los Angeles Kings on October 1, 1984. Two seasons later, he made his NHL debut on October 11 against the Islanders. Just four nights later, he scored his first goal against the Detroit Red Wings. In his rookie season he dressed for 75 games, scoring 13 goals and 38 points and was named an All-Rookie Team defenceman. In 1987-88, Duchesne had 55 points and followed that up the following year with 75 points to lead all Kings' defensemen in scoring and was selected to play in his first NHL All-Star Game.

On May 30, 1991, Duchesne was traded to the Philadelphia Flyers and that season, he led all Flyers' defencemen in scoring with 18 goals and 38 assists for 56 points.

Duchesne was traded again in 1992, in what will go down in NHL history as one of the biggest deals ever. He, along with Ron Hextall, Kerry Huffman, Mike Ricci, the rights to Peter Forsberg, a first-round draft pick, cash and future considerations was moved to the Québec Nordiques for Eric Lindros. The deal obviously had an immediate impact on the Nordiques as the club improved 52 points to make the playoffs for the first time in six years. It also marked the third time Duchesne was selected to the mid-season All-Star Game.

On January 23, 1994, Duchesne was traded to the St. Louis Blues and not too long after, on August 4, 1995, Duchesne was traded yet again, this time to the Ottawa Senators.

Duchesne always seemed to gravitate to Los Angeles, and greatly enjoyed his time with the Kings, so he re-signed with them as a free agent in July 1998, but after just 60 games, his second tour of duty ended in L.A. when he was traded to the Philadelphia Flyers for the second time in his career.

Duchesne was a free agent signing with the Detroit Red Wings in the fall of 1999. He played in his 1,000th career game on October 15, 2000 and went on to play three seasons with the Wings and realized a life long dream of winning the Stanley Cup in his final year in 2002.