With Ben Smith out, Josh Ioane moved to fullback, providing Bryn Gatland an opportunity to start at first-five.
Ioane wore the No 10 jersey during the opening two weeks and he wasn't able to inject himself into the contest enough from a different position.
As could be expected given the personnel turnover, the Highlanders were inaccurate and their attack didn't flow.
They were also unable to gain the ascendancy upfront, which compiled their problems.
First five-eighth Quade Cooper had a hand in a couple of the Rebels' early tries, while Will Genia was typically combative and delivered swift service from halfback.
There was plenty of heat in this one, and the tone was set from kick-off as the mercury soared to 32 degrees.
The Highlanders had the better of the opening quarter as they enjoyed plenty of possession but they probably didn't put enough points on the board.
Then it was their defence that let them down as the Rebels ran in three tries to take a 19-12 advantage to the break.
Often the whipping boys of Super Rugby, the Rebels look to have a bit more steel about them this season, particularly in the forwards.
Throw in exciting backs Tom English, Jack Maddocks and Dane Haylett-Petty and they have the makings of a side that might not be the easy beats of previous campaigns.
The Rebels built on their halftime advantage as a try to Bill Meakes early in the second spell proved decisive.
The Highlanders fought back with a late try to lock Jackson Hemopo but it wasn't enough.
Melbourne were guilty of trying to sit on their lead in the second half and kicked away far too much ball but they can worry about that in the post-match video session.
The win marked the first time the Rebels had beaten a Kiwi Super Rugby side since 2015 as they moved to 2-0 for the season.
The Highlanders will travel to Wellington to meet the Hurricanes next Friday, while Melbourne while host conference rivals the Brumbies on the same evening.
Rebels 24 (Tom English 2, Jack Maddocks, Bill Meakes tries; Quade Cooper 2 con)
Highlanders 19 (Shannon Frizell, Siate Tokolahi, Jackson Hemopo tries; Bryn Gatland con, Marty Banks con)