Having looked in fine form in her 6-3 6-1 win over American Madison Brengle on the opening day, hopes were high for the Egyptian to reach her first third round match at a Grand Slam event.
And Sherif, seeded 54, started well, taking the first set 6-3.
But her Russian opponent fought back, taking the second 6-4.
Sherif, 27, had been trailing in that set but clawed her way back – only to lose her serve at 4-5.
Potapova pushed on to dominate the final set 6-1.
Despite the defeat, it has been a good clay-court season for Sherif who looked impressive on her way to reaching the quarter-finals of the Madrid Open earlier this month, beating Caroline Garcia and Elise Mertens on the way.
The Egyptian was stopped by eventual champion Aryna Sabalenka but her efforts lifted her to a career-high ranking of 43 before she slipped to her current position of 54 heading into Roland Garros.
In 2020, Sherif became the first Egyptian woman to reach the main draw of a Grand Slam at the French Open. She reached the second round in Paris last year before injury forced her to pull out.
