Galatasaray broke the deadlock with a close-range finish from Alexandru Cicaldau at minute 12 at Ali Sami Yen Sports Complex.
The Lions doubled the lead at the 30th minute with an own goal by Marseille's Croatian defender Duje Caleta-Car.
In minute 64, Sofiane Feghouli scored his team's third goal as Kerem Akturkoglu provided the assist for Feghouli.
In the 83rd minute, Marcao dribbled the ball on a counter-attack to assist Dutch star Ryan Babel, who came off the bench just seconds ago.
Babel took a classy shot to beat goalie Pau Lopez.
Olympique Marseille's Polish forward Arkadiusz Milik scored two goals in the 69th and 85th minutes for Marseille.
Galatasaray are currently three points ahead of second-place Lazio with 11 points.
Marseille are in the third spot with four points, while Lokomotiv Moscow are bottom of Group E with two points.
In the last match of the group, Galatasaray will need at least a draw to advance to top-16 of the UEFA Europa League as group winner.
