Milos Raonic suffers cramp in US Open defeat to qualifier Ryan Harrison

America's Harrison is ranked 120th in the world but he took full advantage of his opponent's discomfort to win 6-7 (4/7) 7-5 7-5 6-1.

Raonic, seeded fifth, had been among the favourites to be crowned champion at Flushing Meadows, after an excellent season that has included reaching the semi-final at the Australian Open and the final at Wimbledon.

The Canadian, however, was hamstrung by cramp, which he said was brought on by anxiety, and it was Harrison who booked his place in round three.

"It was probably just nerves and stress, a mental sort of over-exuberance," Raonic said.

"Cramping in the left arm, right forearm there towards the end of the third set, both quads, a little bit in the hip flexor on the left. It was just catching me all over."

Raonic added: "I couldn't switch grips from one point to the next. There were a few points where I would hold the racquet with my left hand and trying to stretch out my right hand in between shots, and that's not going to work."

Raonic becomes the biggest casualty of the US Open so far but it could prove a breakthrough win for Harrison, who was once considered a rising star of American tennis.

Dropping to 197th in the world in 2014, the 24-year-old said a crisis meeting with his parents earlier this year has helped to turn the tide.

"I met with my family. I met with my dad, my fiancee, people close to me," Harrison said.

"I talked to them just about starting to develop a series of matches in a row where emotionally I was able to be selective about when I was getting excited.

"If I did get irritated, it wasn't at the wrong times and it wasn't taking me out of the match. It was just a decision to be resilient out there in the moment."