Federer was eliminated before the semifinals for the second time in past three Grand Slam tournaments, but only the fifth time in the past nine years at a major event. Tsonga was responsible for two of the losses he also beat Federer in the quarterfinals at Wimbledon in 2011.
"I'm pretty sad about the match and the way I played," Federer said. "He was in all areas better than me today. That's why the result was pretty clean."
Serena Williams narrowly averted Federer's fate. She came from behind in the third set and advanced to the French Open semifinals for the first time since 2003 when she defeated Svetlana Kuznetsova 6-1, 3-6, 6-3.
Williams had been beaten the last four times she reached the Roland Garros quarterfinals, most recently in 2010. The 15-time Grand Slam champion, who is ranked No. 1, won her only French Open title in 2002.
"I just got tired of losing in the quarters," she said. "I was so determined to get through that, and I really, really, really, really wanted it more than I think anyone. So I think that kind of helped."
Tsonga earned his first berth in the Roland Garros semifinals and is trying to become the first Frenchman to win the tournament since Yannick Noah in 1983. He's the first Frenchman to reach the semifinals since Gael Monfils in 2008.
"I can't have better a dream," Tsonga told the center court crowd. "So far I play very well. I played against a champion today, a guy who has won everything. Today it's my turn."
On Friday he'll play No. 4-seeded David Ferrer, who beat fellow Spaniard Tommy Robredo 6-2, 6-1, 6-1.
Tsonga was runner-up to Novak Djokovic at the 2008 Australian Open, his best Grand Slam result. Ranked No. 8, he dominated Federer with his blend of power and athleticism.
"Give some credit to the old Jo-Willy Tsonga, please," Federer said.
Federer took a 4-2 lead but played like a mere mortal after that as the match rapidly slipped away. He blew three overheads, missed several easy volleys, hit no aces, dropped serve six times and took a shot to the body on the point that put Tsonga ahead to stay in the final set.
Facing a break point, Federer sliced a drop shot, and Tsonga raced forward to scoop it up. He whacked a backhand that clipped the net cord and then drilled Federer under his right arm.
That made it 4-3, and Tsonga quickly won the final two games. When he closed out the victory, Federer greeted him with a gracious smile and a congratulatory pat on the stomach.
A jubilant Tsonga then went spinning across the court, waving his arms as the partisan crowd roared. Federer, long a fan favorite in Paris, also earned a lusty cheer as he headed to the exit. He responded by applauding the crowd.
"I should have won the first set," Federer said. "Unfortunately I couldn't regroup."
The last time Federer lost to a player ranked so low in a major tournament was at Wimbledon two years ago, when the No. 19-ranked Tsonga overcame a two-set deficit to beat him.
The French Open has always been the most difficult major event for Federer. He won his lone Roland Garros title in 2009 to complete a career Grand Slam and tie Pete Sampras' record of 14 major titles.
Now 31, he has yet to win any tournament in 2013, his longest drought to start a year since 2000.
Williams is also 31 but playing at her peak although that wasn't the case for a long stretch against Kuznetsova. Williams overcame an inconsistent serve, erratic groundstrokes and a 2-love deficit in the final set, winning five consecutive games and then closing the victory with a forehand winner and a scream.
"Yes!" she hollered.
It was the first real test of the tournament for Williams, who lost 10 games after losing a total of 10 games in her four earlier matches. She laughed at herself, screamed at herself, violently shook her uncooperative racket and cocked it over her head, threatening to fling it before she changed her mind.
Williams finally found a way out of her funk and into the semifinals. She extended her career-best winning streak to 29 consecutive matches.
In a post-match on-court interview, Williams seemed spent.
"I'm very happy to have won this quarterfinal because the whole night I was afraid of my quarterfinal match," she told the crowd in French. "It was a very tough match today, but it's good for me because, I don't know, but it's very good. I am exhausted."
Kuznetsova said strained an abdominal muscle early in the tournament, which hampered her serve, but her aggressive returns kept pressure on Williams.
"I did push her to the limit I think today, even without my serve," Kuznetsova said. "I was serving like, I don't know, a grandmother."
Williams is the first American woman to reach the French Open semifinals since Jennifer Capriati in 2004. Her opponent Thursday will be 2012 runner-up Sara Errani, who advanced by beating No. 4 Agnieszka Radwanska 6-4, 7-6 (6).
Williams is 5-0 against Errani.