This loss snapped his 23-match winning streak. After a week off, Pospisil and his partner Adil Shamasdin won the doubles title at the Challenger Britania Zavaleta. In mid-March 2010, Pospisil was the top seed in singles at the Canada F3 in Sherbrooke. He lost only one set in capturing his fifth ITF tour title, defeating Raonic, the second seed, in the final, in three sets. In the second week of April 2010, Pospisil won the doubles title of the Abierto Internacional del Bicentenario Leon, partnering Santiago González as the top-seeded pair. In August 2010, Pospisil lost in the first round of qualifying for the Rogers Cup to eventual qualifier Illya Marchenko. He played doubles in the main draw as a wild card, partnering Raonic. Together, in the first round, they became, and remain, the only team to ever defeat the doubles team of Rafael Nadal and Novak Djokovic. This was his first win in an ATP Tour main draw event. After two weeks off, he, as the tournament top seed, took the singles title at the ITF Mexico F6, defeating fifth seed David Rice in the final. Pospisil won a second consecutive singles title, Mexico F7, by defeating second seed Adam El Mihdawy in the final. In October 2010, Pospisil again was the top seed in singles at Canada F5 in Markham, Ontario and captured the title, defeating fifth seed Nicholas Monroe in the final. It was the eighth Futures singles title of his career. At the midway point of 2011, Pospisil captured three Challenger doubles titles and two Futures titles, including one in singles. In March at the Rimouski Challenger, he won the doubles title partnering Treat Conrad Huey. Two weeks later, Pospisil captured the doubles title of USA F8 partnering Nicholas Monroe. Two weeks later, in April, he won his third straight doubles title, the 2011 Tallahassee Tennis Challenger playing with Bobby Reynolds. In May 2011, Pospisil won his ninth career ITF Futures singles title, Korea F2. In June 2011 at Wimbledon, attempting to qualify for a Grand Slam tournament for the first time, Pospisil lost in the second round. The following week, he teamed with Reynolds, as the second seeds, to capture the title of the Jalisco Open.