The second generation of the Foligno family to suit up for the Sabres, Marcus followed his father, Mike, (1981-90) to Buffalo. Foligno also followed his father's footsteps in junior hockey, playing from 2007-11 with Sudbury of the Ontario Hockey League.

The Sabres selected Foligno in the fourth round (No. 104) in the 2009 NHL Draft after he scored 12 goals and finished with 30 points in 65 games during the 2008-09 season. In 2010-11, Foligno finished third on the team in scoring with 59 points. He was selected as the best body checker in the Eastern Conference in the OHL Coaches Poll and was named to the league's Second All-Star Team.

Making his international debut at the 2011 IIHF World Junior Championship in Buffalo, Foligno, a Buffalo native, scored two goals and four points in seven games as Canada won the silver medal.

Foligno began the 2011-12 season with Rochester of the American Hockey League and in 60 games led the team with five game-winning goals. He was named Rochester's rookie of the year.

Recalled on four occasions Foligno finished with six goals and 13 points in 14 games for the Sabres in 2011-12. His NHL debut was a family affair, Dec. 20, 2011, against the Ottawa Senators and older brother Nick. Foligno enjoyed a five-game point streak from March 10-19, 2012, including his first NHL goal March 10, 2012, at Ottawa, and his first multipoint game on March 14, 2012, against the Colorado Avalanche.

He was the third player in Sabres history to record seven or more points in his first six career games, joining Phil Housley (nine) and Ray Sheppard (seven). Foligno's 26.1 percent shooting percentage led the Sabres. He was named the NHL's Rookie of the Month for March 2012 after posting six goals and 11 points in 11 games.

During the 2012-13 season, Foligno finished third on the Sabres with 108 hits. He logged a four-game point streak from Jan. 27-Feb. 2, 2013, and scored twice against the New York Rangers on March 12, 2013. He scored in three straight games, from Dec. 11-15, 2014, to highlight his 2014-15 season. Foligno also enjoyed a pair of three-point nights during the 2015-16 season and scored an NHL career-high 13 goals in 2016-17.

The Sabres traded Foligno to the Minnesota Wild on June 30, 2017, and he was reunited with Nick Foligno when his older brother was sent to the Wild by the Chicago Blackhawks on March 6, 2026. Earlier that season, Marcus scored his first NHL hat trick to help Minnesota defeat the Toronto Maple Leafs 6-3 at Scotiabank Arena on Jan. 19.

Marcus won the 2026 King Clancy Memorial Trophy presented "to the player who best exemplifies leadership qualities on and off the ice and has made a noteworthy humanitarian contribution in his community," which Nick won while with the Columbus Blue Jackets in 2016-17. They teamed with the NHL, the NHL Players' Association, the Wild, Blackhawks and the V Foundation for Cancer Research to create the Foligno Face-Off, which raised funds for breast cancer research in honor of their mother, Janis Foligno, who died from breast cancer in 2009. As the winner, Marcus Foligno received a $25,000 donation to benefit a charity or charities of his choice.