Mbappe gave PSG a taste of what they would be missing if he left for Real Madrid, who have made bids to recruit the France striker since Messi joined on a two-year deal from Barcelona.
PSG are top of the standings with a maximum 12 points.
All 20,545 tickets available were sold at the Auguste Delaune stadium to see 34-year-old Messi play and the fans, who chanted the Argentina forward's name, were rewarded in the 66th minute when he replaced the disappointing Neymar.
Mbappe did not disappoint though in a brilliant performance, seemingly unfazed by the transfer frenzy surrounding him.
Two days before the end of the window, the 22-year-old made the difference with his speed and sense of timing, opening the scoring with a header and rounding off with a clinical finish.
After a stuttering start, PSG got into their groove and Mbappe put them ahead after 15 minutes by heading home from Angel Di Maria's cross.
PSG somehow got too comfortable and Reims started to apply some pressure, with Moreto Cassama's superb strike hitting Keylor Navas's crossbar three minutes before the break.
Reims celebrated what they thought was a Marshall Munetsi equaliser five minutes into the second half, only for the Zimbabwean's effort to be ruled out for offside.
Messi started to warm up after 57 minutes, drawing applause from the Reims supporters, whom he saluted.
They sang his name just when he was about to come on, shortly after Mbappe had doubled PSG's advantage from Achraf Hakimi's cross at the end of a sharp counter attack.
Mbappe combined with Messi, but the former Barcelona striker was not in the same condition as the Frenchman, having not played a competitive game since winning the Copa America with Argentina on July 10.
Earlier, French champions Lille finally got their title defence going with a 2-1 home win over Montpellier and surprise package Angers beat visiting Stade Rennes 2-0 to go second on 10 points.
Lille celebrated their first league win of the season thanks to goals from Yusuf Yazici and Jonathan David. Montpellier ended the match with 10 men after defender Junior Sambia was sent off late in the second half.
Promoted Clermont Foot continued to impress as they kept their unbeaten record intact after fighting back from two goals down in a 2-2 home draw with Metz. They are third on eight points from their first four matches.