Cronulla coach Craig Fitzgibbon has swung the axe after last week's heavy loss to the Warriors, dropping Matt Moylan and co-captain Wade Graham as the Sharks fight to retain their top-eight spot.
Elsewhere, Latrell Mitchell and Reece Walsh return for a battle of marquee fullbacks in round 21 and Penrith welcome Nathan Cleary back from his hamstring injury.
Fitzgibbon has been loyal to a core group of players all season and previously resisted the urge to make significant changes to his side following the 54-10 loss to Melbourne last month.
But after Cronulla yet again fell to a top-eight rival on the weekend, Fitzgibbon sprung into action and dropped the two veterans, both of whom were exposed defensively in the 44-12 defeat.
Braydon Trindall has been recalled to play five-eighth in Moylan's place against Manly on Sunday, while Connor Tracey comes into the centres at the expense of the benched Siosifa Talakai.
Jesse Colquhoun has been promoted the starting side for only his seventh NRL game after Teig Wilton went down with a knee injury against the Warriors.
The Sharks, who were running third only a week ago, could fall to eighth spot with a loss to the Sea Eagles.
Mitchell will play his first NRL game in two months when South Sydney fight to keep pace with the top eight against Brisbane this weekend.
The fullback injured his calf late in NSW's camp for the State of Origin series opener and while he was initially expected to line up in Origin II, the injury has prevented him from playing ever since.
The Rabbitohs have won only two of six games during Mitchell's lay-off and fallen from first on the ladder after 11 rounds to eighth after 20.
Souths were similarly patchy when Mitchell went down with a hamstring injury last season but just as their hold on the top-eight appeared tenuous, the Rabbitohs have named the marquee man to face second-placed Broncos.
He is joined in the side by centre Campbell Graham, who returns from a sternum injury.
"(Mitchell) has come back a lot fitter and slim, he's going to be a dangerous man come Friday night," said Rabbitohs centre Isaiah Tass.
Mitchell's rival fullback Walsh returns from suspension for Brisbane, who also welcome Payne Haas back from the ankle injury that kept him out of Origin III.
Cleary had been ready to line up against the Dolphins on Sunday but the Panthers opted to give him one more week's rest and will re-inject him in the clash against Canterbury on Sunday.
Canberra prop Josh Papali'i is back from a hamstring injury to face the Warriors, while Ofahiki Ogden has been named to start in place of the suspended Reagan Campbell-Gillard for Parramatta's clash against North Queensland.
