That set up a semifinal showdown with France’s 361st-ranked Lois Boisson.
The second seed Gauff battled past her fellow American 6-7 (6/8), 6-4, 6-1 in a tense last-eight clash littered with a whopping 14 double-faults and 101 unforced errors.
“It means a lot, especially getting through this tough match today, it wasn’t an easy match and I’m very happy to get through it,” Gauff said.
“I’m so excited to be in the semifinals back here again and have a lot more work to do. Just savour this one today and then next one tomorrow.”
Keys came through a tense first set in a tie-break after blowing a 4-1 lead with a double-break, but Gauff upped her level enough to fight back.
The 21-year-old was the runner-up to Iga Swiatek in a one-sided showpiece match in 2022.
Keys had been hoping to challenge for a second consecutive Grand Slam title, but failed to reach the semifinals in Paris for a second time.
Boisson, meanwhile, continued her dream run at Roland Garros, defeating world number six Mirra Andreeva to advance to the final four.
Boisson won a thrilling battle 7-6 (8/6), 6-3 against Russian Andreeva. (AFP)