With Messi and Neymar not judged ready for Saturday's (AEST) game by Mauricio Pochettino, Mbappe scored his first of the season with what was just his fourth headed goal in Ligue 1, and his first since 2017.
Mbappe put PSG 2-0 up, with Ander Herrera having opened the scoring, but Keylor Navas's error handed Brest a reprieve.
Idrissa Gueye's long-range strike seemed to have settled the contest, though it was ultimately substitute Angel Di Maria who had to wrap up the points after Steve Mounie had pulled another one back.
Mbappe's six attempts across the opening two Ligue 1 games failed to yield reward and the France star might have done better in the fourth minute, with his close-range shot saved well by Marco Bizot, though an expected goals (xG) figure of 0.065 suggested it was a difficult chance.
With Marco Verratti also going close, PSG's dominance told when Herrera tried his luck with a volley which crept in under Bizot, who did better to stop Achraf Hakimi doubling PSG's tally.
Little blame could be attached to Bizot soon after, however, with Mbappe charging in to get his head on a loose ball and divert a looping effort into the right-hand corner.
Navas had to hold his hands up at the other end before half-time, with PSG's shot-stopper failing to prevent Franck Honorat, the benefactor of Romain Faivre's exquisite flick, scoring despite getting a hand on the shot.
PSG's frustrations grew as it looked to add to its lead, yet Bizot's vulnerability from long shots came to the fore again as Gueye's dipping effort from 35-yards out evaded his grasp.
Navas atoned for his earlier mistake by denying Ronael Pierre-Gabriel, though Mounie did set up a grandstand finish with a cool 85th-minute finish.
There would be no fairytale comeback, however, with Di Maria – just nine minutes into his return – lobbing Bizot on the break to seal the points.
PSG is away again at Reims before the international break, meaning Messi's debut may still well come on the road. It seems likely, with Mauro Icardi having gone off injured late on. Brest faces Strasbourg in its next outing.