Reims were under pressure for much of Friday's Ligue 1 clash at the Stade Louis II, and were fortunate to only be one down when Moukandjo was brought off the bench with half an hour remaining.
However, Monaco were left to rue their failure to convert their dominance into more goals when the Cameroon international - who played for the principality club in the 2010-11 season - slotted past Danijel Subasic in the 80th minute.
Leandro Jardim's hosts began the game on the front foot, and Elderson Echiejile gave them a deserved lead when he rounded off a smart passing move 20 minutes in.
Bernardo Silva raced down the right and sent a low ball to the back post, where the Nigerian was on hand to convert his first goal of the season from a tight angle.
Monaco continued to pile forward after the opener, with teenager Anthony Martial at the forefront of their attacks.
The 18-year-old was denied a goal by Mohamed Fofana when he scuffed beyond keeper Johnny Placide, only for the Reims defender to clear his goal-bound effort.
And Martial went close again soon after, as his fierce drive from inside the area forced Placide into a good save at his near post.
There was no let-up in the home side's dominance after the break, but their lack of cutting edge in the final third cost them dear.
A swift Reims counter with 10 minutes remaining ended with Moukandjo side-footing beyond Subasic from Nicolas de Preville's perfectly weighted cross from the right.
