Quinta was appointed coach of the newly promoted side midweek following the departure of Ricardo Cheu, who oversaw Penafiel's poor start to the season.
Penafiel - promoted from the Segunda Liga after finishing third last term - lost their opening four matches of the campaign.
But under Quinta they finally earned their first points of the season, thanks to goals for Helder Guedes and Andre Fontes.
Guedes opened the scoring in the 11th minute from the penalty spot.
The home side received a boost six minutes into the second half, when Luis Advincula saw red for Vitoria Setubal.
Penafiel made the most of their numerical advantage in the 73rd minute, Andre Fontes converting Dani's cross.
Vitoria Setubal's woes were compounded four minutes later as Manu received his marching orders for a second bookable offence.
Penafiel's first win of the season lifted them out of the relegation zone and into 15th, while Vitoria Setubal are just a point clear of Penafiel.
Also on Saturday, 10-man Sporting Braga came from behind to draw 1-1 at Nacional.
Braga were up against it from the 54th minute following Aderllan Santos' second yellow card.
Hosts Nacional broke the deadlock just two minutes later through Saleh Gomaa and Braga were seemingly beaten.
Jose Ze Luis came off the bench to level with seven minutes remaining, though, as Braga claimed a share of the spoils.
Braga - sixth in the standings with eight points - are three points adrift of league leaders Vitoria Guimaraes.
