Ryan Harrison of the United States celebrates his win over Milos Raonic of Canada during his second round Men's Singles match on Day Three of the 2016 US Open at the USTA Billie Jean King National Tennis Center on August 31, 2016 in the Flushing neighborhood of the Queens borough of New York City. (Photo by Elsa/Getty Images)

American Ryan Harrison has caused the first major shock of the US Open, defeating No.5 seed Milos Raonic in four sets, 6-7, 7-5, 7-5, 6-1.

It is Harrison's biggest win of his career and the first time he has advanced to the third round of a Grand Slam.

The 24-year-old will now face Cypriot Marcos Baghdatis, after he defeated Benoit Paire, 6-2, 6-4, 3-6, 6-4.

However, Harrison was aided by Raonic's lack of mobility, after the big serving Canadian required treatment on an upper left leg complaint midway through the third set.

Earlier in the match, he also received treatment on a wrist injury.

His leg issue caused the most discomfort, limiting his power on serve.

Harrison took full advantage, winning nine of the last 11 games to advance to the third round.