Massimo Bruno gave Anderlecht the lead in the 42nd minute before Omar Govea equalised for Mouscron on 52 minutes.
But with 10 minutes remaining, Onyekuru scored what proved to be the winner for Anderlecht.
“Pleased to score the winning goal. Thankful,” Onyekuru wrote on his verified Twitter handle.
The former Eupen player who is on loan at Anderlecht from Everton, has now scored seven goals in 14 league appearances.
He made his official debut for the Super Eagles in their final Group B match of the 2018 FIFA World Cup qualifiers against Algeria on November 10 which ended 1-1. He came on as a second half substitute, replacing Anthony Nwakaeme.