Novak Djokovic suffered a shocking first-round defeat at the US Open, losing to unseeded Argentine Mariano Navone in a dramatic five-set battle in New York.

The 39-year-old Serbian, who entered the tournament chasing a record 25th Grand Slam singles title, went down 7-6(5), 5-7, 4-6, 6-2, 6-1 after a gruelling four-hour, 36-minute contest.

Djokovic made a strong start and moved ahead early in the opening set, but Navone fought back and forced a tiebreak before taking the first set. The Serbian responded by winning the next two sets and appeared to have regained control.

However, physical problems began to affect Djokovic as the match progressed. He vomited during the third set and later struggled with a back issue that appeared to affect his serve and movement.

Navone capitalised on Djokovic’s physical difficulties, taking the fourth set and dominating the deciding set to complete the biggest victory of his career.

The result ended Djokovic’s hopes of extending his Grand Slam record to 25 major titles. It was also his earliest exit from a Grand Slam tournament since the 2006 Australian Open.

For Navone, ranked 49th in the world, the victory was a career-defining moment. The Argentine admitted that defeating Djokovic, whom he regards as one of the greatest players ever, felt like a dream.

Djokovic, a four-time US Open champion, acknowledged the difficult experience after the match as his remarkable run at Flushing Meadows came to an unexpected end.