[6] In his first season with the UMass Amherst Minutemen in 2013–14, he made just one appearance, debuting against the University of Vermont Catamounts in the 2014 Hockey East Tournament.

[5] However, UMass Amherst was knocked out of the 2015 Hockey East Tournament by the Notre Dame Fighting Irish, ending his college career.

[6] Undrafted by teams in the National Hockey League (NHL), Vatrano forwent his senior year of college in 2014 to pursue a professional career, signing a three-year entry-level contract with the Boston Bruins on March 12, 2015.

[7] He signed an amateur tryout contract with Boston's American Hockey League (AHL) affiliate, the Providence Bruins, making his professional debut to finish out the 2014–15 season.

[17] He also won the Willie Marshall Award for the league's leading goal scorer and was named to the AHL's First All-Star and All-Rookie teams.

[18] Vatrano was returned to the AHL for the 2016 Calder Cup playoffs as the Providence Bruins faced the Wilkes-Barre/Scranton Penguins in the first round.

[5][19] Prior to the start of the 2016–17 Boston Bruins season, Vatrano had suffered an unexpected injury to his left foot due to torn ligaments that required surgery to repair.

[5] Vatrano began the 2017–18 season with Boston, and was among the young forwards on the team expected to add supporting offense to the Bruins' star players.

[30] He then saw increased time as a healthy scratch due to roster regulations in which he could be lost on waivers that prevented him from being assigned to the AHL.

[5] On February 22, 2018, the Bruins traded Vatrano to the Florida Panthers in exchange for a third-round pick in the 2018 NHL entry draft.

[33] He scored in his debut with the Panthers on March 10, ending his 13-game goalless drought, to help the team record their eighth straight home win.

He also set a new NHL career high with four points in one game as the Panthers beat the San Jose Sharks 6–2 on January 21.

[5][50] When play resumed for the 2020 Stanley Cup playoffs, the Panthers faced the New York Islanders in the qualifying round.

[51] Ahead of the playoffs, Panthers coach Joel Quenneville chose to place Vatrano back on the first line with Barkov, with whom he regularly played with on the penalty kill unit.

[5][54] Entering the pandemic-delayed and shortened 2020–21 season, Vatrano had become more of a complete player, regularly appearing on the penalty kill and second power play units.

[5] The Panthers made the 2021 Stanley Cup playoffs and faced their cross-state rivals, the Tampa Bay Lightning in the first round.

[5] In the final season of his three-year contract in 2021–22, Vatrano was considered on of the key depth scorers for the Panthers team.

[5] On March 16, 2022, Vatrano was traded by the Panthers to the New York Rangers in exchange for a conditional 2022 fourth-round draft pick in an effort to clear cap space to acquire another defenseman.

He made his Rangers' debut on March 17 in a 2–1 loss to the New York Islanders, playing on a line with Ryan Strome and Artemi Panarin.

[66][67] He immediately found chemistry with the Rangers, playing alongside former junior teammates Jacob Trouba and Andrew Copp.

[5] In the 2022 Stanley Cup playoffs, he helped the Rangers advance to the Eastern Conference Finals, losing the the Tampa Bay Lightning, contributing with 5 goals and 13 points through 20 post-season games.

[5][70] As a free agent from the Rangers, Vatrano was signed to a three-year, $10.95 million contract with the Anaheim Ducks on July 13, 2022.

[77] Entering the final year of his contract, general manager Pat Verbeek resisted attempts by other teams to acquire Vatrano in the offseason.

[77] That night, he recorded another three-point effort, scoring two goals and an assist in a 4–1 win over the Tampa Bay Lightning.