Waratahs boss Michael Cheika has made four changes to his starting XV for Friday's clash with the Rebels in Sydney.
Sekope Kepu will start at loosehead prop, the franchise's biggest ever player, Will Skelton, returns at lock, pushing Jacques Potgieter to flanker and captain Dave Dennis to number eight.
Benn Robinson slips back to the replacements bench to allow fellow Wallaby Kepu his first run on start of 2014.
"I just wanted to try this combination, I thinks Keps has played well and was unlucky to miss out in the first place," Cheika told the Waratahs' official website.
"He's done what he needs to do to force his way back in the side."
Kepu isn't about to let his coach down, promising: "I'll leave no stone unturned to get it right."
He packs down alongside Paddy Ryan and hooker Tatafu Polota Nau, who'll become the sixth most capped Waratahs player in history, when he takes to the field on Friday night.
In the reshuffled pack, Skelton will join the durable Kane Douglas at lock, whilst the back row will comprise blindside flanker Potgieter, Michael Hooper, who earns his 50th Super Rugby cap at openside, and Dennis at the base of the scrum.
If he comes on from the bench, Wycliff Palu will earn his 99th cap against Melbourne.
"We've got to make sure we use Cliff correctly and he'll definitely contribute at the back end of the game," added Cheika.
Scrum-half Nick Phipps takes on his old franchise for the first time in Super Rugby, since joining the Waratahs at the start of this season.
"I've got a lot of friends down there but it won't be any different to playing any other Australian franchise," said Phipps.
In the midfield, Bernard Foley will wear the 10 jumper and Kurtley Beale, also lining up against his old team-mates, will wear number 12. Adam Ashley-Cooper is at outside centre and the back three of Peter Betham, Alofa Alofa and Israel Folau remains the same.
Of the two teams' six previous meetings, the 'Tahs had been unbeaten until last season when the Rebels recorded their first ever win to send the Weary Dunlop Shield to Melbourne.
Waratahs: 15 Israel Folau, 14 Alofa Alofa, 13 Adam Ashley-Cooper, 12 Kurtley Beale, 11 Peter Betham, 10 Bernard Foley, 9 Nick Phipps, 8 Dave Dennis (c), 7 Michael Hooper, 6 Jacques Potgieter, 5 Kane Douglas, 4 Will Skelton, 3 Paddy Ryan, 2 Tatafu Polota Nau, 1 Sekope Kepu.
Replacements: 16 Tolu Latu, 17 Jeremy Tilse, 18 Benn Robinson, 19 Wycliff Palu, 20 Stephen Hoiles, 21 Brendan McKibbin, 22 Rob Horne, 23 Matt Carraro, 24 Pat McCutcheon, 25 Jonno Lance.
Date: Friday, March 21
Venue: Allianz Stadium, Sydney
Kick-off: 19.40 local (08.40 GMT)
Referee: Jaco Peyper (South Africa)
Assistant referees: Rohan Hoffmann (Australia), Graham Cooper (Australia)
Television match official: George Ayoub (Australia)