McDonald has played only six games after missing 51 with a concussion.
Kevin Shattenkirk, Jason Arnott and David Perron also scored, and Alex Pietrangelo had three assists to help the Blues move within three points of NHL-leading Detroit with 77 points.
Brian Elliott made 26 saves, allowing only Frans Nielsen's goal.
The Blues have points in a team-record 20 straight home games (17-0-3) and have 25 home wins, one more that the Red Wings for most in the league (25-3-4).
The Islanders' road winning streak ended at four.
Nielsen gave the Islanders a 1-0 lead just 59 seconds into the game, corralling his own rebound when his initial shot was blocked by Shattenkirk, then lifting the puck over Elliott.
The Blues came back with two goals to grab a 2-1 lead on goals by Arnott and Shattenkirk.
Arnott was able to lift a shot in tight over Montoya's left shoulder with 5:20 left in the period to tie it. Then, on their first power play of the game, Shattenkirk's first goal in 16 games on a one-timer squirted through Montoya with 2:48 left in the period for a 2-1 lead. Backes supplied the screen in front.
The Blues kept up the pressure in the second, with McDonald getting his first of the season for a 3-1 lead, but the key sequence came at the other end.
Elliott's key pad stop on Jay Pandolfo prevented the Islanders from tying the game, and the Blues were on the attack with an odd-man rush. Montoya stopped Jamie Langenbrunner's initial shot, but McDonald crashed the goal and backhanded the rebound in at 2:53.
The Blues showed no mercy to Montoya, who was a surprise starter when Evgeni Nabokov was a late scratch with the flu. Perron's tip of Pietrangelo's shot from the right point 8:52 into the period made it 4-1, making the Blues a perfect 2-for-2 on their first pair of power plays.
Oshie tipped Pietrangelo's point shot from the slot through Montoya's pads with 5:07 left for the Blues' fifth goal on only their 19th shot of the game.
NOTES: The Blues are the only team in either conference to be unbeaten in regulation against the opposing conference. They are 12-0-2 against the East and 13-0-2 dating to last season. ... Arnott (shoulder) and D Kent Huskins (ankle) were activated from injured reserve Thursday. ... After earning 21 points in 12 straight games, Islanders C John Tavares has two assists in eight games. ... The Islanders were the last Eastern Conference team to beat the Blues in regulation.