This comes after the first-round fall of Rafael Nadal, and a second-round defeat of Roger Federer. But Williams had won 34 consecutive matches prior to Wimbledon and was thought to be unbeatable. The loss ends Williams' Grand Slam winning streak.
On Monday, Sabine Lisicki sent Williams home in the fourth round, 6-2, 1-6, 6-4. Williams had just won the French Open and had been a 1-2 favorite prior to Wimbledon.
"I didn't play the big points good enough," Williams said. "I didn't do what I do best.
"Sabine played really well, she always does well at Wimbledon, so I knew it would be a tough match going in. Definitely had opportunities, but I didn't take them."
Lisicki, No. 23, has defeated French Open champions at Wimbledon for the last three years, and four times in the five past years.
"I'm so happy," a teary Lisicki said after the match.
"I was fighting for every single point and hanging in there. It's unbelievable."