The host side made the perfect start when Lyon midfielder Thiago Mendes was adjudged to have handled the ball in the box. After a lengthy VAR delay, Payet stepped up and confidently dispatched the ball into the top corner.
Marseille enjoyed the vast majority of possession and chances in the first half, and eventually doubled their advantage on the 39th minute. Payet again influential, picking the ball up and arrowing a shot into the bottom corner for his third goal of the season.
Lyon rallied in the second half and grabbed a goal back on the hour mark. Moussa Dembele headed home when Marseille goalkeeper Steve Mandanda and defender Alvaro left Traore's cross for each other.
Marseille was soon retuced to ten men when Spaniard Alvaro was sent off just minutes later for hauling down Dembele with the striker clean through on goal.
But OM managed to hold on despite some late Lyon pressure, with Martin Terrier blasting the final chance wide in the 90th minute.
The result leaves Lyon 14th in the standings, just four points away from the relegation zone.