Fatih Terim's men fought back from a goal down to lift the Turkish top-flight crown for the second time in a row.
Rijad Bajic's effort in the 17th minute broke the deadlock to put Istanbul Basaksehir ahead but the hosts proved their resilience to fight back in the second half.
Two minutes after the restart, former West Ham midfielder Sofiane Feghouli scored with a spectacular bicycle kick to level the match.
Onyekuru then headed home from close range in the 64th minute to earn Galatasaray the victory and spark jubilant scenes amongst the home supporters.
The win leaves Galatasaray 69 points from 33 games, three points more than Istanbul Basaksehir with a game to go. When points are tied, the Turkish league uses the head-to-head record instead of goal difference so Galatasaray's title is confirmed.
For head coach Fatih Terim it is a second Super Lig triumph in a row and eighth with the club in total, spread over four spells stretching back to 1996.
It means Galatasaray are champions in Turkey for a 22nd time, extending their record as the most successful side in the competition. Fenerbahce are next on the list with 19 titles ahead of Beskitas, who have won the league on 15 occasions.
Terim's men will hope to end their campaign on a high when they visit Sivasspor for their last league outing of the season on May 25.
Onyekuru, on a season-long loan from Everton, is Galatasaray’s top scorer this campaign with 14 goals and there is speculation about whether the club will be able to keep the player next season, either on-loan or via a permanent transfer.
On the international scene, Onyekuru has been named in Nigeria's 25-man provisional squad for the 2019 Africa Cup of Nations while Feghouli is expected to play a part in Algeria's campaign at the continental showpiece.