Manly led 10-6 at halftime and dominated the opening 15 minutes of the second period, looking well set for a seventh successive win and their first over a top-four side this season.
But thanks to some brilliant defending, including a try-saver from Greg Inglis on David Williams and a Steve Matai effort that was adjudged to have been held up, Souths somehow found a way back into the game.
And it was in no small part down to the efforts of man-of-the-match Reynolds.
Just shy of the hour mark Reynolds found touch from a goalline dropout, then produced a superbly-weighted grubber-kick to force a restart, and from the resulting set Nathan Merritt crossed for his 150th NRL try.
That four-pointer well and truly turned the game on its head as Souths, after two successive defeats, rediscovered the form that's kept them on top of the ladder for much of the season to keep Manly pegged back in their own half.
Giant prop George Burgess was kept out from close range, as was Inglis, returning from a knee injury, but the Manly defensive wall finally collapsed in the 68th minute when the Queensland superstar dived over to put his side in front with Reynolds adding the extras.
That setback rocked Geoff Toovey's side and their incisive attacking earlier in the game deserted them and Andrew Everingham iced the result three minutes from time after being put clear by Dylan Walker.
Tries from Jamie Lyon and Jorge Taufua had helped Manly open up a first half lead, either side of a Chris McQueen effort.
Souths' Jeff Lima was placed on report for a spiteful ankle twist on Anthony Watmough who made a shock return to action after initially being ruled out with a knee injury.
In the second half Manly's Justin Horo was also sanctioned for a high tackle on Inglis.
Manly coach Toovey was furious with the performance of the officials and could find himself in hot water with the NRL after unloading on referees Shayne Hayne and Henry Perenara.
Toovey was angry at the decision to not award a try to Matai when the scores was 10-6 in the second half.
"Unless I am blind and I can see the ball on the ground then what was the decision?" Toovey said.
"Can someone answer me that? He (video ref) said held up but the ball's on the ground. How can that be held up?
"That's ridiculous. There's got to be an investigation into this, someone's got to be accountable for this."
Souths coach Michael Maguire said his side showed great character to turn the game around after being on the back foot for the opening 15 minutes of the second half.
"We got off to a rocky old start but what the boys have found is that will to work hard," Maguire said.
"They were prepared to commit to what they did well to stop two or three tries in the second half.
"And it's full credit to the team."
SOUTH SYDNEY 22 (D Farrell G Inglis C McQueen N Merritt tries A Reynolds 3 goals) bt MANLY 10 (J Lyon J Taufua tries J Lyon goal).
Referees: Shayne Hayne, Henry Perenara.
Crowd: 20,060 at Bluetongue Stadium.