Melbourne have scored four tries against the unbeaten Super Rugby Pacific leaders, but the Chiefs recovered from a poor start to record a 44-25 win in Hamilton.
The Chiefs scored six tries of their own and picked up a fourth straight bonus-points win, while the Rebels dropped to 1-3.
Melbourne scored the first eight points of the contest, but conceded the next 27.
They scored the last try of the first half and got back to 27-15 by halftime, but the home side crossed twice in the first five minutes after the restart to pull away again.
Melbourne lost centre and Wallabies utility back Reece Hodge to an injury early in the game.
Rising five-eighth Carter Gordon was prominent in the Rebels' good start after Hodge notched the first points of the game with a penalty goal.
A well-timed pass from Gordon put Hodge through and he beat two players before being pulled down just short of the line.
Melbourne recycled and a long cutout pass from Gordon found captain and flanker Brad Wilkin, who put hooker Alex Mafi over in the corner.
The Chiefs got on the board through a penalty to five-eighth Bryn Gatland and Gordon came close to adding another try with a fine solo run, before he was tackled by fullback Shaun Stevenson close to the line.
The hosts retained possession better in latter part of the opening half and unlocked the Rebels' defence, scoring three tries.
A great run down the right from Emoni Narawa set up inside centre Rameka Poihipi, and he returned the favour for the former with a good chip kick which the winger gathered and just managed to stay inside the field of play before touching down.
The rampaging Chiefs added another try when Stevenson raced onto a kick, toed the ball through and won the chase.
Melbourne got a much needed score before the break when centre Stacey Ili crossed after good work from Gordon and winger Lachie Anderson.
Any hopes of a full-scale Rebels revival were dashed when prop Tyrone Thompson burrowed over less than two minutes into the second half, and Stevenson pounced on a loose ball to score his second three minutes later.
Melbourne continued to complete and fullback Nick Jooste scored their third try, with Gordon again involved in the buildup.
The Chiefs responded again through winger Etene Nani-Seturo, crossing after the ball was quickly transferred from one side to the other after they turned it over in Rebels territory.
Wilkin was held up over the line and the Rebels created other opportunities but poor handling and options stymied them until replacement David Feliuai barged over.
