After Jeff Cowan gave Vancouver a 1-0 lead at 7:07 of the first period, the Ducks responded by scoring three times - twice by McDonald - on their first nine shots against goalie Roberto Luongo. Teemu Selanne had a goal and assist during the outburst, and Chris Kunitz assisted on all three goals.
Jean-Sebastien Giguere finished with 26 saves for the Ducks.
Ryan Getzlaf gave Anaheim a three-goal pad midway through the final period, and McDonald capped the scoring on a shot from just left of the crease when the Ducks had a two-man advantage with 52 seconds remaining.
The second game is Friday night in Anaheim before the best-of-seven Western Conference semifinal series shifts to Vancouver for games Sunday and Tuesday.
Luongo faced 31 shots as the Ducks kept the pressure on by crowding in front of the Vancouver goal. He was replaced by Dany Sabourin after Getzlaf's goal, and Sabourin gave up McDonald's third goal.
After starting the game relatively slowly and with the Canucks on the attack for the first few minutes, the Ducks quickly shook off the rust.
Anaheim hadn't played since wrapping up the opening series against Minnesota last Thursday. The Canucks didn't really get a day off. They had taken a 3-1 lead in the series against Dallas, but lost the next two before finally concluding the series with a Game 7 win on Monday night. Tuesday was a travel day.
Posting the first multi-goal and four-point game of his playoff career, McDonald scored his second goal of the night to give the Ducks a 3-1 lead at 19:11 of the opening period.
On a 2-on-1 rush, Selanne skated down the right side, waited for the defender to commit toward him, then slid the puck across to McDonald. The Ducks' centre beat Luongo with a shot between the pads.
Selanne put Anaheim ahead with a nifty move across the crease. Cutting through the right circle, Selanne took McDonald's pass from behind the goal line, sliced around a defender and beat Luongo with a wrist shot to the stick side.
McDonald's first goal came on a power play during a scramble in front. Luongo blocked Chris Pronger's shot from the blue line but McDonald controlled the puck. With traffic in front, Luongo had little chance to stop McDonald's shot.
Notes: McDonald's and Kunitz's three points in the first period tied a Ducks' record for points in a period in the playoffs. Selanne had a goal and two assists in the second period last year against Colorado. Kunitz had a career-best three assists and set the team record by recording them in one period. ... The Ducks won three of four games between the teams during the regular season. ... Along with not getting time off since eliminating Dallas, the Canucks came off a series when they played three overtime games - a total of 92:15 extra minutes.