The Bulls were without three starting midfielders in Monday night's clash at Campbelltown Stadium, after losing Anthony Caceres, Chris Ikonomidis and Sime Grzan to gastro.
That trio had picked up the illness in Vietnam, where the Bulls drew 1-1 with Cong An Hanoi FC in the ACL Two last Thursday.
Attacking midfielder Liam Rose stood tall in their absence to open the scoring against Adelaide - captained by Craig Goodwin - in the 11th minute, as Socceroos coach Tony Popovic watched on.
Jonny Yull hit back for the Reds before halftime, but Ji Dong-Won restored the lead in the 64th minute to fire Macarthur to their first win of the season.
After entering the second home-and-away round dead last in 12th without a point, Macarthur move to eighth (1-1) and will face Western Sydney next week.
Meanwhile, Adelaide remain sixth (1-1) on goal difference ahead of next round's clash against Auckland FC.
Rose opened the scoring with his career-first goal in 124 games after Reds defender Bart Vriends gave away possession in an attempt to clear the ball out of Adelaide's box.
Macarthur goalkeeper Filip Kurto added to the highlight reel after pulling off two critical saves within less than 10 minutes, but Adelaide continued to pepper the goal.
It was Yull - in his 50th match - who beat Kurto a minute into added time and buried the ball after a cross from Ethan Alagich before the break.
Adelaide would have been unlucky to finish the first half without scoreboard reward after locking most of the play inside their attacking half to take nine shots to Macarthur's five.
The second half looked set to play out in similar terms after the Reds continued to keep Macarthur on the backfoot.
But the home side were able to rally as Harrison Sawyer sprung to life to direct the attack, with Ji finding the back of the net after a Luke Brattan corner.
Socceroos star Goodwin was desperate to salvage a point for the Reds but failed to make the most of his chances.