When the St. Louis Blues named Pietrangelo as captain on Aug. 24, 2016, he became the latest defenseman to have that honor, a group that includes Chris Pronger, Al MacInnis, Al Arbour, Barclay Plager and Eric Brewer.

Pietrangelo was certainly a worthy choice after leading the Blues in blocked shots (136) in 2015-16 and helping them reach the Western Conference Final for the first time since 2001. In 2014-15 he became the first defenseman in team history to finish with at least 40 points in each of his first four full NHL seasons.

His high point as Blues captain came on June 12, 2019, when he scored what proved to be the Stanley Cup-winning goal in a 4-1 victory against the Boston Bruins at TD Garden in Game 7 of the Final, then received the Cup from NHL Commissioner Gary Bettman. It capped a playoff run that saw Pietrangelo finish with 19 points (three goals, 16 assists) in 26 games and help the Blues win their first championship since entering the NHL in 1967.

Success has followed Pietrangelo throughout his hockey career, including after he signed a seven-year contract with the Vegas Golden Knights on Oct. 12, 2020. He became the second player in NHL history to score a Cup-clinching goal against a coach and later win a championship with him in the same role (Bruce Cassidy), the Golden Knights winning the Stanley Cup with a five-game victory against the Florida Panthers in the 2023 Stanley Cup Final. Cy Denney did the same against Art Ross in 1927 and playing for Ross in 1929.

Pietrangelo had two assists in his 1,000th NHL game when the Golden Knights lost 5-3 to the Minnesota Wild at T-Mobile Arena on Feb. 12, 2024. He was the fifth active defenseman to get  a point in his 1,000th game, joining Ryan Suter (two assists), Brent Burns (one goal), Drew Doughty (one assist) and Marc-Edouard Vlasic (one assist). It was another accomplishment in a journey that includes the 2009-10 Ontario Hockey League final, being named a three-time OHL all-star and playing in the 2008 CHL Top Prospects Game. He also won a gold medal with Canada at the 2009 IIHF World Junior Championship and silver at the event in 2010, when he was named the tournament's best defenseman. At the 2011 IIHF World Championship, he finished with five points in seven games and was again named top defenseman.

Selected by the Blues with the No. 4 pick in the 2008 NHL Draft, Pietrangelo made his NHL debut Oct. 10, 2008, against the Nashville Predators. His first full NHL season was 2010-11, when he led Blues defensemen in points (43), plus-minus rating (18) and shots on goal (161).

In 2011-12 Pietrangelo ranked fifth among NHL defensemen in points (51) and first in game-winning goals (six). That season he also became the youngest defenseman (22) in Blues history to have consecutive seasons of 40 or more points and became the second defenseman in St. Louis history to score at least six game-winning goals and six power-play goals in the same season. Pietrangelo finished fourth in voting for the Norris Trophy, awarded to the top defenseman in the NHL.

Pietrangelo ranked first in the NHL in 2012-13 with 32.4 shifts per game, and he led the Blues in shorthanded ice time per game (3:01) and power-play ice time per game (2:51), becoming the first defenseman to do so since MacInnis in 2002-03.

In 2013-14 Pietrangelo and Nashville's Shea Weber were the only NHL defensemen to score at least 50 points and play more than 200 power-play and shorthanded minutes.