PSG, awarded the Ligue 1 title on a points-per-game basis after the season was called off in April, made it a double through Neymar's 14th-minute effort but it proved a pyrrhic victory.
Loic Perrin was sent off in the 31st minute following a cynical tackle on Mbappe, who was withdrawn with an apparent ankle injury and later returned to the bench on crutches with his leg in a brace, making him a serious doubt for PSG's return to Champions League action next month.
That challenge sparked a huge melee in the first competitive match in France since March, watched by a small crowd at the Stade de France, with PSG - who also lost Thilo Kehrer to injury - seeing out the win despite a spirited effort from 10-man Saint-Etienne.
Denis Bouanga almost gave Claude Puel's side an early lead when he rattled the post, but it was Neymar who broke the deadlock, turning in from close range after Jessy Moulin palmed away Mbappe's strike.
Moulin produced a brilliant save to deny Angel Di Maria before Perrin scythed down Mbappe as he was about to burst away, sparking unsavoury scenes as the two sets of players squared up.
Referee Amaury Delerue gave the defender his marching orders following a look at the pitch-side monitor after initially showing him a yellow card and another four players were booked - including PSG substitute Marco Verratti for coming off the bench to show dissent - due to the reaction to a tackle that left Mbappe limping down the tunnel following treatment.
Bouanga volleyed over as Les Verts on the hour-mark as Les Verts went in search of an equaliser and heavy tackles continued to define a frantic encounter.
Moulin denied Mbappe's replacement Pablo Sarabia as a second goal eluded PSG, but Neymar's early effort proved to be enough for Tuchel's men to regain the trophy.
What does it mean? Another trophy but concerns for Mbappe
While it was mission accomplished for PSG, winning a trophy they missed out on with a defeat to Rennes in the final last year for the 13th time in their history, the dominant force in French football's latest triumph came may have come at a huge cost.
The sight of Mbappe on crutches will give Tuchel a huge headache ahead of Champions League quarter-final against Atalanta on August 12.
PSG face Lyon in the Coupe de la Ligue final next Friday, but European glory is the priority and a potential Mbappe absence could derail their hopes.
Neymar continues scoring streak
Brazil forward Neymar scored four goals in three friendly matches before the long-awaited return to competitive action.
The former Barcelona man was quiet by his standards, but he showed his predatory instincts to pounce from close range for the winner.
Rash Perrin fails to lead by example
Defender Perrin's lunge cost his side, who had looked dangerous going forward but were always going to be up against it after he was given his marching orders.
Les Verts lacked discipline in a match they had waited so long for and Perrin could have no complaints about his dismissal.
PSG will be looking to put another trophy in the cabinet when they come up against Lyon next week, while the beaten finalists return to friendly action against Troyes on Monday.