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.