Melbourne playmaker Quade Cooper worked his magic to help the Rebels maintain their unbeaten start to the season.
In a heart-stopping finish, the Highlanders looked for a match winner in the 78th minute as flanker Shannon Frizell tried to plant the ball down over the line, but the Television Match Official (TMO) ruled he had dropped it.
The Rebels set up the victory with four classy tries, all scored by their backs.
Cooper showed off his array of skills to set up two of those as he settled into his new AAMI Park home.
His game wasn't perfect, also throwing a first-half intercept and a loose ball late in the match which gave the Highlanders a crack.
Earlier in the day, Wallabies coach Michael Cheika talked up Cooper's chances of a recall to the Australian fold and said he'd been impressed by the efforts of the Reds' discard.
"He played a smart game in the first game out, he played nice and flat and he was very active in organising the play. But also looking to attack himself a little bit ... always with the flair that he brings to the game," Cheika said in a video released on Friday by Rugby Australia.
"There is great opportunity tonight for him, and just keep banging it. And with that, I have no doubt he will come into strong contention for selection."
Cooper only enhanced his case by popping a no-look flat pass for winger Jack Maddocks to score in the 26th minute.
And, early in the second half, he put a stabbing kick into the in-goal which wrong-footed Highlanders five-eighth Bryn Gatland and bounced into the arms of centre Billy Meakes for Melbourne's fourth try of the night.
The Highlanders, who rested All Blacks Ben Smith and Aaron Smith, drew first blood in the third minute through Frizell after a perfect cross-field kick from Gatland.
However, Rebels centre Tom English hit back soon after, scoring the first of two opening-half tries.
The visitors closed the gap to five points in the 64th minute through hard- working lock Jackson Hemopo and continued to hammer the Rebels until Frizell's late effort came up short.
The Highlanders now have two wins and a loss.