Nicknamed "Chief", Berube played 17 seasons in the NHL for the Philadelphia Flyers, Maple Leafs, Calgary Flames, Washington Capitals and New York Islanders.

Berube additionally served as a national team scout for Canada at the 2016 World Cup of Hockey, under Blues general manager Doug Armstrong.

He made his NHL debut on March 22, 1987, recording 16 penalty minutes which included two fighting majors, in a 3–1 Flyers win over the Pittsburgh Penguins.

The Flyers traded him to the Edmonton Oilers along with Craig Fisher and Scott Mellanby for Dave Brown, Corey Foster, and Jari Kurri on May 30.

Four months later he was traded to the Toronto Maple Leafs along with Glenn Anderson and Grant Fuhr for Vincent Damphousse, Peter Ing, Luke Richardson, and Scott Thornton on September 19.

Berube played the first half of the 1991–92 season with Toronto before he was traded again on January 2, 1992 to the Calgary Flames along with Alexander Godynyuk, Gary Leeman, Michel Petit, and Jeff Reese for Doug Gilmour, Jamie Macoun, Kent Manderville, Ric Nattress, and Rick Wamsley.

[4] Berube was named the head coach of the Philadelphia Phantoms, the Flyers' affiliate in the American Hockey League, before the 2006–07 AHL season.

On October 22, 2006, Bob Clarke resigned from his position as general manager of the Flyers, and head coach Ken Hitchcock was released from his duties.

[6] On June 29, 2016, Berube was named the head coach of the Chicago Wolves in the American Hockey League, the affiliate of the St. Louis Blues.

[12] On June 24, the Blues dropped the "interim" tag from Berube's title and officially named him as the 26th head coach in franchise history, with a three-year contract.