Two tries from centre Michael Collins and 12 points from the returning Gareth Anscombe inspired a second-half Ospreys comeback in the United Rugby Championship win against Dragons.
Dragons built a 16-10 half-time lead with a Josh Lewis try and 11 points from Sam Davies.
Collins' double, a Luke Morgan try and Anscombe's boot inspired the revival for Toby Booth's men.
A late Rhodri Williams try gave Dragons a losing bonus point.
Watching Wales head coach Wayne Pivac would have been an interested observer in the form of Collins and Anscombe before the autumn international series.
Joining from the Highlanders in New Zealand, Wales-qualified utility back Collins has returned to Welsh rugby after a stint with the Scarlets in 2015-16.
Anscombe finally made his competitive Ospreys debut after signing for the region in 2019 from Cardiff.
He suffered a serious knee injury playing for Wales against England in August 2019 and it was 761 days before he returned to the rugby field in a pre-season friendly against Northampton earlier this month.
Wales lock Will Rowlands made a significant physical impression on his Dragons debut alongside props Aki Seiuli and Mesake Doge, scrum-half Lewis Jones and wing Jordan Olowofela.
Collins, Tomas Francis and Jac Morgan also made official Ospreys debuts.
Opposing captains Ross Moriarty and Rhys Webb were in the thick of the action early on. Dragons' Moriarty was in possession when he drove Webb with the Ospreys scrum-half going off for a head injury assessment, temporarily replaced by Reuben Morgan-Williams.
The hosts capitalised on the reshuffle with Sam Davies grubber kick allowing full-back Josh Lewis to score the opening try.
Ospreys' early woes continued when Wales centre Owen Watkin was yellow carded for illegally lifting Ollie Griffiths out of a ruck before Davies added a penalty.
Webb returned and made an immediate impact with a smart pass to find Collins on a clever angle to allow the centre to carve through the Dragons defence as Anscombe converted.
Ospreys continued to pay for indiscipline as Davies slotted over another penalty and a drop-goal before Anscombe responded with three points as the home side led 16-10 at half-time.
The visitors made a positive second-half start with Anscombe reducing the deficit to three points. A nudge kick through from Dan Evans was collected by livewire wing Matt Protheroe before Dragons centre Jack Dixon was yellow-carded for a cynical professional foul.
The Webb-Collins partnership worked again and as the centre cantered over unopposed as Ospreys led for the first time.
Anscombe and replacement Tiaan Thomas-Wheeler combined to release wing Morgan for the Ospreys third try as the Dragons conceded 14 points with 14 men.
Rowlands had been an imposing Dragons physical presence for before Ospreys brought on British and Irish Lions lock Adam Beard from the replacements bench.
Beard was expected to miss the opening few weeks of the season after his Lions exploits in South Africa this summer, but is the first Welsh tourist to return.
Dragons responded with an opportunist try from replacement scrum-half Rhodri Williams to set up a frantic finale, but Ospreys held on for victory.
Ospreys head coach Toby Booth: "We are delighted with the outcome. It is a very hard place to come and Welsh derbies are tough.
"We had a crowd which everybody was excited about and we needed to quell them and early on we did everything but.
"We found a way and I was happy with the way we came back into the contest which we could have easily let go and to get across the line was encouraging."
Dragons director of rugby Dean Ryan: "I was really pleased with elements of the performance, especially in the first half.
"We were very accurate and in possession we looked very dangerous with lots of ball carriers, especially with that back row and Will Rowlands.
"The disappointment is pretty obvious, that 25-minute shift of momentum when we didn't really understand how to wrench it back. We've got to get better in those moments."
Dragons: Josh Lewis; Jonah Holmes, Jack Dixon, Aneurin Owen, Jordan Olowofela; Sam Davies, Lewis Jones; Aki Seiuli, Ellis Shipp, Mesake Doge, Will Rowlands, Ben Carter, Ross Moriarty (capt), Ollie Griffiths, Aaron Wainwright.
Replacements: Richard Hibbard, Greg Bateman, Chris Coleman, Joe Maksymiw, Taine Basham, Rhodri Williams, Jamie Roberts, Ioan Davies.
Ospreys: Dan Evans; Mat Protheroe, Michael Collins, Owen Watkin, Luke Morgan; Gareth Anscombe, Rhys Webb (capt); Nicky Smith, Sam Parry, Tomas Francis, Bradley Davies, Rhys Davies, Will Griffiths, Jac Morgan, Morgan Morris.
Replacements: Elvis Taione, Rhodri Jones, Tom Botha, Adam Beard, Ethan Roots, Reuben Morgan Williams, Josh Thomas, Tiaan Thomas-Wheeler.
Referee: Sam Grove-White (SRU)
Assistants: Gwyn Morris & Tom Spurrier (WRU)
TMO: Sean Brickell (WRU).