Paire, the world number 47, recorded a shock 6-3, 6-4 win at the Crandon Park Tennis Centre to inflict a third consecutive defeat on Djokovic.

The 30-year-old, a 12-time Grand Slam champion, is ranked 12th after returning from an elbow injury at the Australian Open in January.

He has now lost three matches in a row since reaching the fourth round of the opening Grand Slam of the season, where he was beaten by South Korean Chung Hyeon.

Djokovic then succumbed to a surprising reverse at the hands of qualifier Taro Daniel of Japan at the Indian Wells Masters earlier this month.

Paire will go on to face another Serbian in Filip Krajinovic in round three after he beat Britain's Liam Broady 6-3, 6-2.

Elsewhere in the men's draw, Portugal's Joao Sousa produced a superb display to knock out seventh seed David Goffin of Belgium.

Sousa claimed a straightforward 6-0, 6-1 victory to progress to the third round, where he will meet American Jared Donaldson.

Donaldson joined the Portuguese in booking a place in round three as he dispatched 25th seed Feliciano López of Spain 6-4, 6-2.

Argentina's Juan Martin del Potro is also through as the Indian Wells Masters winner overcame Dutchman Robin Haase 6-4, 5-7, 6-2.

Kei Nishikori of Japan, who defeated Australia's John Millman 7-6, 4-6, 6-3, awaits for Del Potro in the next round.

In the women's draw, defending champion Johanna Konta of Britain began her campaign with a 6-4, 6-4 win over Kirsten Flipkens of Belgium.

Konta, the 11th seed will take on Flipkens' compatriot Elise Mertens in the last 32 after she ousted Bernarda Pera of the United States 7-6, 6-3.

Ukraine's Elina Svitolina was among the other winners as the fourth seed defeated Japan's Naomi Osaka, who won the Indian Wells title and beat Serena Williams in the first round in Miami, 6-4, 6-2.