In a game devoid of both teams' first-choice halfbacks due to State of Origin, it was Manly who missed their playmaker more at CommBank Stadium.
Eels debutant Joash Papalii was the fairytale story of the night with a try-assist and try in back-to-back sets, in front of 150 of his family and friends.
Parramatta's forwards also dominated Manly's forwards, with the Sea Eagles disjointed in defence on both edges.
Manly are a side of wild extremes even with their best players on the park, able to beat the NRL's top teams one week before falling to cellar-dwellers the next.
But in the Sea Eagles' first game without Cherry-Evans since he announced in March he was leaving the club at season's end, his absence was clearly felt.
Manly's attack lacked any real flow or strike with Luke Brooks and Jake Arthur in the halves, while Cherry-Evans' usual dangerous right edge fell silent.
Overlooked NSW star Tom Trbojevic had a hand in two Lehi Hopoate tries down the left in the first half, but that constituted all of Manly's scoring.
The Sea Eagles then barely looked like throwing a punch in the second half, with their best chance coming when Hopoate was pushed out before grounding a ball.
"We lacked cohesion tonight," coach Anthony Seibold said.
"For whatever reason we just didn't look like we have been when we were at our best.
"We were so good last week against the Cowboys away from home, defensively and grittiness. And then tonight we were the total opposite."
Friday night's loss is by no means a clear picture of what the Sea Eagles will look like next year, with Canberra's Jamal Fogarty signed on a three-year deal.
But it was a clear sign of how much the Sea Eagles still rely on the most-capped halfback in the club's history, after the contract drama that has overshadowed their season.
Worryingly for Manly, they also still have two games to play without Cherry-Evans this year in pre-Origin rounds.
Parramatta, in contrast, still played with great flow without halfback Mitch Moses.
Stand-in halfback Dean Hawkins had a role in four tries, including putting Jack Williams over for one when he set up to go deep and instead went short to the forward.
"That's Footy Dean, God love him," coach Jason Ryles said.
"It was good to give him another opportunity to come in in that situation. He does all the little things really well and it's good to see him get the reward.
"We've still got a long way to go, it's a slow burn. It's just good the last six weeks we're starting to look like on the field, not just training."
Papalii had a debut to dream of, throwing the last pass for a Jordan Samrani pass after coming on for a concussed Will Penisini early.
The 20-year-old Papalii then scored in the corner on the next set after a Dylan Walker break as the Eels went from 4-0 down to 10-4 up in the blink of an eye.
Isaiah Iongi also looked good again at fullback, and put the Eels 12 points up after halftime when he dummied and slid past Brooks to score.
The win means Parramatta will not finish the round in last place, guaranteed to stay above the loser of Penrith and Newcastle and just one win outside the top eight.
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