The Red Wings, who had been outscored 12-4 in losing three of their previous four games, jumped into a 2-0 lead on goals by Bertuzzi 1:10 into the first period and Danny Cleary at 3:10.
David Krejci cut that to 2-1 at 17:53 of the first with his first goal in 21 games, but the Red Wings regained control in the second period when Jiri Hudler, Zetterberg and Bertuzzi all beat goalie Tuukka Rask.
Rask played his second game in the Bruins' last eight. They beat the Montreal Canadiens 8-6 with the NHL's top goalie, Tim Thomas, in net. On Friday, Thomas replaced Rask to start the third.
Despite their second loss in six games, the Bruins remained three points ahead of the second-place Canadiens in the Northeast Division. The Red Wings increased their lead in the Central Division to seven points over the Nashville Predators, who beat them 4-1 on Wednesday night.
In that loss, Detroit goalie Jimmy Howard left the game after allowing four goals on Nashville's first 16 shots. The Red Wings avoided their third shutout in four games when Ruslan Salei scored his first goal of the season in his 53rd game with Detroit with 3:58 left in the second period.
On Friday, the offense was much more productive as the Red Wings led 5-1 with 3:22 remaining in the second.
Bertuzzi began the scoring when he took a pass from Zetterberg and scored off the right post. Just 2 minutes later, Cleary scored his 17th goal of the season on a pass from Hudler, who fed the puck from behind the net and into the slot where Cleary had gotten behind defenseman Dennis Seidenberg.
Rask, who allowed goals on Detroit's first two shots, received a mock cheer when he made a routine save about four minutes into the game.
Krejci scored his eighth goal on a power play. Zdeno Chara's shot from the right point went wide to the left of the net, where Milan Lucic collected it then passed to Krejci in the slot.
A nice pass from Zetterberg set up Hudler's sixth goal at 1:09 of the second period. Detroit's scoring leader made a backhand pass from the left circle to Hudler, who one-timed the puck past Rask from the right corner of the crease.
The game settled down with neither team scoring for more than 15 minutes. Detroit then scored twice within 24 seconds for a 5-1 lead.
Zetterberg's 17th goal made it 4-1 at 16:14 of the second when he ended Detroit's 0-for-18 power-play streak. Then Bertuzzi got his 10th goal at 16:38 as Rask mishandled a puck to his right, leaving it behind the net. As Rask scrambled back toward the crease, Bertuzzi shot the puck off the back of the goalie's pad and into the net.
Tomas Holmstrom finished the scoring with his 12th goal on a power play with 6:09 left in the game.
Notes: The Red Wings hadn't played in Boston since Nov. 29, 2008. They'll host a rematch with the Bruins on Sunday afternoon. ... Bertuzzi's second goal was his 700th career point. ... Krejci's goal was his first since he scored two at Florida on Dec. 27. ... Bruins F Tyler Seguin, the No. 2 overall pick in the draft, was a healthy scratch.