Wawrinka sealed a stunning 7-6 (8/6), 5-7, 6-4, 3-6, 8-6 victory with a magnificent winner from yards behind the baseline after five hours and nine minutes on Court Suzanne Lenglen.
He has a 23-3 losing head-to-head record against close friend and fellow Swiss Federer.
“It's incredible, lots of emotions. Thanks to all the fans for staying and (the) support,” said the 34-year-old Wawrinka after the third longest match in the last 20 years at the French Open.
5 hours, 9 minutes. 1 amazing tennis match.@stanwawrinka outlasts Tsitsipas 7-6(6) 5-7 6-4 3-6 8-6 to reach the quarter-finals at Roland-Garros.
— Roland-Garros (@rolandgarros) June 2, 2019
“It's for these kind of emotions that I live for after coming back from injury.”
It is the first time Wawrinka has reached a Grand Slam quarter-final since losing to Rafael Nadal in the 2017 Roland Garros final, and completes an amazing turnaround from 12 months ago.
Last year, the three-time Grand Slam champion, following injury struggles, lost in the first round to Guillermo Garcia-Lopez and dropped out of the world's top 250.