In the biggest victory of his life, Tsonga knocked off Federer, the third seed and a former world No. 1, 3-6, 6-7 (3-7), 6-4, 6-4, 6-4 on Wimbledon's center court. Their match went 3 hours, 8 minutes with Tsonga edging Federer 18-17 on aces and recording three breaks to Federer's one.
"I was two sets down and I break. I did a good game of return and after that it was just amazing," Tsonga said. "I just played unbelievable, served unbelievable and now I'm here, I'm in semifinal and I can't believe it."
The Swiss star had been 178-0 when winning the first two sets of a Grand Slam match.
"It's kind of hard going out of the tournament that way, but unfortunately it does happen sometimes," Federer said. "At least it took him sort of a special performance to beat me, which is somewhat nice."
Tsonga and Djokovic will meet in Friday's semifinals, while Nadal will play Murray the same day.
Nadal, ranked No. 1 in the world, won his 19th straight match at the All England Club with a 6-3, 6-3, 5-7, 6-4 victory over 10th-seeded American Mardy Fish on Court 1.
Djokovic, seeded second, earned a 6-2, 3-6, 6-3, 7-5 victory over 18-year-old Aussie qualifier Bernard Tomic.
Murray breezed by unseeded Spanish lefthander Feliciano Lopez 6-3, 6-4, 6-4.