Kiefer Sherwood had a goal and an assist, Elias Pettersson had two assists, and Kevin Lankinen made 26 saves for the Canucks (10-6-3), who had lost two in a row. Max Sasson had an assist in his NHL debut.
Tim Stutzle scored his 100th NHL goal, Claude Giroux had a goal and an assist, Drake Batherson had two assists, and Linus Ullmark made 17 saves for the Senators (8-11-1), who are 0-4-1 during their losing streak.
Vancouver defenseman Quinn Hughes received a game misconduct and five-minute major for boarding Josh Norris at 12:29. The Canucks killed off the entire five-minute power play.
DeBrusk tipped in a Conor Garland wrist shot on the power play to give the Canucks a 1-0 lead at 18:36 of the first period.
Ottawa is 1-10-1 when allowing the first goal this season.
Brady Tkachuk tied it 1-1 at 3:41 of the second period with a power-play goal. He tipped a Jake Sanderson point shot, gathered the rebound and tucked it in around Lankinen's right pad.
Teddy Blueger responded to make it 2-1 at 9:23. He took a centering pass from Sasson and beat Ullmark low glove with a wrist shot from the slot.
DeBrusk took a cross-ice pass from Sherwood and finished a deke on the backhand around Ullmark's outstretched left pad on the rush to make it 3-1 at 13:01.
Sherwood pushed it to 4-1 at 8:41 of the third period when he pounced on a loose puck in the crease.
Giroux chipped the puck over Lankinen's glove in tight on the power play with Ottawa's net empty to cut it to 4-2 at 16:29.
Stutzle one-timed a cross-slot pass from Giroux to cut it to 4-3 with 44 seconds remaining.