Belgium international Thomas Meunier returned to a youthful PSG side while Mbappe was benched as the visitors’ quest for two wins in as many games got off to a poor start.
Guingamp held their own in front of a vociferous home crowd in the first half of the Ligue 1 fixture.
They forced an impressive save from goalkeeper Gianluigi Buffon to deny Marcus Thuram in the 14th minute.
Guingamp winger Marcus Coco capitalised on PSG right back Colin Dagba’s error and played in striker Nolan Roux, who slotted past Buffon to give the hosts a shock lead.
Guingamp continued to pile on the pressure as PSG struggled with defensive errors and lacked attacking fluidity.
France international Mbappe replaced Timothy Weah at the start of the second half as PSG took control of the match.
Neymar won a penalty kick in the 53rd minute and converted it to equalise.
A resurgent PSG then dominated proceedings and created numerous chances before Mbappe scored his opening goal of the season in the 82nd minute.
He soon doubled his tally to seal the win.
Striker Radamel Falcao missed a penalty kick as a wasteful AS Monaco were held to a goalless draw with LOSC Lille in their first home league match of the season.
Monaco, the only team to win the league title other than PSG in the last five seasons, failed to convert their chances in the opening half.
Lille, meanwhile, rarely troubled Diego Benaglio’s goal.
Skipper Falcao, who notched a goal and an assist in Monaco’s opening victory at Nantes, missed the hosts’ best chance in the 67th minute, when he won a penalty kick.
But he failed to convert it as Lille goalkeeper Mike Maignan pulled off a good save.
Monaco continued to push for a breakthrough but Lille held on to secure a point.
PSG top the standings, followed by Dijon and Stade Reims, who climbed to third after Friday’s 1-0 win over Olympique Lyonnais.
Monaco and Lille are fourth and fifth while a second consecutive defeat left Guingamp in 17th position.