Djokovic won two matches in Dubai before losing to VeselyNovak Djokovic will lose his number one ranking after being beaten 6-4 7-6 (7-4) by Jiri Vesely in the quarter-finals of the Dubai Tennis Championships.
The tournament was Djokovic's first of 2022 after he was not allowed to compete in the Australian Open because he is unvaccinated against Covid-19.
The Serb will now be replaced by Daniil Medvedev at the top of the men's rankings on Monday.
"I never thought I would really have a chance against Novak, said Vesely.
The Czech Republic player, ranked 123 in the world, was broken when serving for the match, before winning the second set tie-break to complete an inspired victory.
"It's an amazing feeling," added Vesely, speaking to Amazon Prime. "He (Djokovic) is one of the greatest of all time if not the best."
Russia's Medvedev will be the first player other than Djokovic, Roger Federer, Rafael Nadal and Andy Murray to rise to the top of the rankings for 18 years.
Djokovic has spent a total of 361 weeks as world number one, which is a record in the men's game.
Vesely beat the 20-time Grand Slam champion in 2016 on the clay of Monte Carlo and repeated the feat on the hard courts of Dubai.
A Djokovic double fault on break point at 3-3 in the opening set gave the initiative to Vesely, who went on to serve out and take command of the match.
At 3-3 in the second, a fierce Vesely backhand saw him break Djokovic, only for the Serb to fight back and level at 5-5.
In the tie-break, however, another Djokovic double fault at 4-3 down proved costly as he slipped to a surprise upset.
Analysis
BBC tennis correspondent Russell Fuller
In the past two and a half years, Daniil Medvedev has consistently piled up the ranking points, won a maiden Grand Slam title and reached three other finals.
Novak Djokovic's absence from the Australian Open accelerated his arrival at the summit, but Medvedev is a very worthy successor.
Exceptional and assertive on hard courts, the 26-year-old showed signs last summer of getting to grips with the clay of Roland Garros and the grass of Wimbledon.
With Masters Series events on the hard courts coming up in Indian Wells and Miami - and Djokovic very likely absent -Medvedev may have some clear road ahead.
But I would not bet for a moment against Djokovic regaining the world number one position in future - and adding to his staggering record of 361 weeks at the top.
