He moved up to the under-18 team, which at the time played in the North American Hockey League (NAHL), where in 43 games, Foligno scored eight goals and 20 points.

It took Foligno 23 games, but he scored his first career OHL goal on November 20, 2004, beating Kitchener Rangers goaltender Dan Turple in a 6–3 loss.

[citation needed] Foligno returned to the Wolves for a third season in 2006–07, as he scored a team high 31 goals and 88 points in 66 games, helping Sudbury clinch a playoff berth.

[citation needed] The Ottawa Senators selected Foligno with the 28th overall pick in the 2006 NHL Entry Draft held in Vancouver, British Columbia.

On March 21, 2007, Senators General Manager John Muckler announced that the team and Foligno agreed to a three-year, entry-level contract.

He spent some time with the Binghamton Senators of the American Hockey League (AHL) during the 2007–08 season, appearing in 28 games, scoring six goals and 19 points.

He began the season with Ottawa and played in his first game on October 3, 2007, earning no points in 7:36 ice time in a 4–3 victory over the Toronto Maple Leafs.

[2] Foligno scored his first career NHL goal and point on October 18, 2007, as he beat Carey Price of the Montreal Canadiens in a 4–3 Senators win.

The Senators were ultimately swept in four-straight games in the Eastern Conference Quarterfinals; Foligno's goal was his only registered point of the series.

[citation needed] Foligno spent the entire 2008–09 season in the NHL with the Senators, scoring 17 goals and 32 points in 81 games.

The Senators qualified for the 2010 playoffs, and in six games, Foligno had one assist as Ottawa again fell to the Pittsburgh Penguins in the Eastern Conference Quarterfinals.

[citation needed] On July 1, 2012, Foligno was traded to the Columbus Blue Jackets in exchange for defenseman Marc Methot.

[4] Having lost two of their starting six defensemen via free agency, Ottawa desperately needed to acquire a defenseman and Methot fit the bill for the Sens.

[6] Foligno scored a notable goal in Game 4 of the Eastern Conference Quarterfinals in the 2014 playoffs against the Pittsburgh Penguins — Blue Jackets forward R. J. Umberger blocked a slapshot with his head, whereupon Foligno picked up the puck, skated down the ice and shot a knuckle-puck past goaltender Marc-André Fleury for the come-from-behind overtime winner.

On February 25, 2016, in a game against the New Jersey Devils, Foligno recorded 4 points, including his second career hat trick, and leading the Blue Jackets to a 6–1 victory.

[11][12] On November 9, 2019, Foligno was assessed a major penalty and game misconduct for elbowing Colorado Avalanche forward Pierre-Édouard Bellemare.

To make the trade work, he was initially dealt to the San Jose Sharks in exchange for forward Stefan Noesen, with Columbus retaining 50% of his salary.

On June 26, 2023, Foligno, a pending free agent from the Bruins, was traded to the Chicago Blackhawks along with Taylor Hall in exchange for Ian Mitchell and Alec Regula.

[23] On January 6, 2024, Foligno was placed on IR with a fractured left finger, which he suffered during a fight with New Jersey Devils' defenseman Brendan Smith.

[29] Foligno is also the "Celebrity Chair" of Cystic Fibrosis Canada's Ottawa Chapter, where he and his wife Janelle are very active participants.