[1] Ference played two more seasons with Portland and had a brief stint in the International Hockey League (IHL) with the Kansas City Blades before joining Pittsburgh in 1999.

The following season, on February 10, 2007, he was traded, along with teammate Chuck Kobasew, to the Boston Bruins for defenceman Brad Stuart and centre Wayne Primeau.

On April 22, 2011, Ference was fined $2,500 for giving the finger to the crowd at the Bell Centre in Game 4 of the playoffs first round series against the Montreal Canadiens after a scoring a goal.

Ference's initial comments after the incident indicated it was an "equipment malfunction,"[2] though he later confessed[3] it had been an intentional gesture following an emotional playoff goal.

[4][5] On June 15, 2011, Ference and the Boston Bruins defeated the Presidents' Trophy-winning Vancouver Canucks 4–0 in Game 7 of the Final to win the Stanley Cup.

[8] On September 29, Ference was named the 14th captain in Oilers NHL franchise history, succeeding Shawn Horcoff, who had been traded to the Dallas Stars.

[11] He however remained on the Oilers long-term injured list for the duration of the 2016–17 season, before formally ending his career at the conclusion of his contract on July 13, 2017.

[14][15][16] Ference's association with environmentalist David Suzuki while in Calgary led him to create a carbon-neutral program for the NHL, which now includes over 500 players who purchase carbon offset credits to counteract the negative environmental impact of professional sports.

[17] In February 2012, National Geographic began a ten-episode Web series called "Beyond the Puck" highlighting Andrew's life as an NHL Player and "eco-warrior.

"[18] On September 5, 2011, following the Bruins Stanley Cup championship, Ference organized and led a parade and flash mob in Boston's North End, which is the area where he resided during the NHL season.