The five-time champion was beaten 3-6, 7-5, 7-6 (7), 7-6 (3) in the round of 16.
He will go on to face Wimbledon champion Djokovic in the last eight as his NY fairy tale continues.
After a routine-looking first set the Australian took advantage of Federer's awful first serve percentage to dictate the play and come back into the match.
The 37-year-old managed to pull off an around-the-net-post forehand victor.
Up 2-1 in the third, Djokovic took an off-court medical timeout, leaving fans to wonder if the veteran might be suffering from a serious ailment.
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Keys, who has made at least the quarterfinals in three of the four Grand Slams this year, fired six aces and had no double faults to dispatch Cibulkova in short order. He was up a break in the second set, before his serve began to betray him.
Djokovic, however, was able to keep his cool just long enough to finish off Sousa with another late break.
Not since Pat Rafter handed a tantrum-throwing Federer a tennis lesson on the then-18-year-old's grand slam debut at Roland Garros in 1999 had an Australian conquered the great Swiss at a major.
Facing much more resistance from the 90-degree heat and 50-percent humidity than from his outclassed opponent, Novak Djokovic figured he can count on cooler conditions during a night match at the U.S. Open his next time out.
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Danny Ward cancelled out Auba's strike before Lacazette netted an 81st-minute victor following some fine work by Lucas Torreira.
Millman pulled off the historic upset over Federer in their fourth round matchup, 3-6 7-5 7-6 (9-7) 7-6 (7-3) to reach the quarter finals of the singles tournament, the first time in his entire career Millman has reached the final stages of a Grand Slam event.
It is the third consecutive appearance that ended one step short of the quarter-finals for the 31-year-old Sharapova, who had been 22-0 under the lights at Arthur Ashe Stadium.
Sousa, who totaled 21 winners to 28 unforced errors, has never taken a set off Djokovic in five career head-to-heads.
Stream every match at the US Open live on the FOX+ app and catch up on highlights of any action you've missed.
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The committee has had access to more than 415,000 pages on Kavanaugh's background, the lawyer said in the letter. Wade , while Only 37% approve of a Brett Kavanaugh confirmation.
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