McDonald was sent back to the VFL after kicking just one goal across the opening two rounds of the season.
But the premiership forward made the most of Ben Brown's absence on Sunday with four goals, 16 disposals, three contested marks and three score assists in his team's 19.12 (126) to 9.9 (63) victory in front of 42,458 fans.
Bayley Fritsch chipped in with three goals, while star midfielders Oliver (34 disposals, 10 clearances, 10 tackles) and Petracca (29 possessions, three goals) dominated after quiet starts.
Brodie Grundy had a field day in the ruck on the way to 22 possessions, 33 hitouts and seven clearances.
The one concern for Melbourne was an injury to defender Jake Lever in the final quarter.
Lever limped off the ground after hurting his left leg while diving forward to tackle Connor West.
Sunday's win improved Melbourne's record to 3-1 and moved them into third on the ladder.
West Coast are now 1-3 and face another season of pain given their injury woes.
The Eagles made seven changes to their team following the injury carnage from last week's western derby, which claimed stars such as Liam Ryan, Jeremy McGovern, Luke Shuey and Jamie Cripps.
West Coast were so short on tall options in defence that returning midfielder Elliot Yeo was forced to play the role of key backman at times.
Tim Kelly tallied a game-high 36 disposals for West Coast to go with five clearances and two goals, while former Demon Jayden Hunt finished with 20 touches and a goal.
There were mistakes aplenty in the first half despite the sunny and still conditions, with both sides guilty of butchering golden chances.
West Coast won the inside 50m count 13-9 in the opening term, but Melbourne's ability to get over the top of the Eagles' defence saw the visitors to skip out to a 17-point lead at the first break.
Fritsch and McDonald booted two goals apiece in the first quarter, and Fritsch had three to his name by early in the second term.
Melbourne's lead was only 19 points late in the second quarter, but the visitors booted seven of the next eight goals to break the contest wide open.
McDonald's fourth goal was the highlight, with the 30-year-old competing hard in a ruck contest in the middle of the ground before running forward to receive a handball and set sail from 52m.
