Djokovic is unable to enter the United States because he is unvaccinated against Covid-19, but he had petitioned US authorities for special permission to enter.
The Indian Wells ATP 1000 event begins next week in the California desert and is followed by the prestigious tournament in Miami which Djokovic is now expected to miss unless US authorities have a change of heart.
The United States still doesn't allow unvaccinated international travellers to enter the country, with the Transportation Security Administration recently indicating the policy would not change until at least mid-April.
Djokovic's vaccination status saw him deported from Australia shortly before the 2022 Australian Open.
After winning Wimbledon he also missed the US Open last year because of the travel restriction.
He returned to Australia in January, winning the 2023 Australian Open for a record-equalling 22nd Grand Slam singles title.
He took his match win streak to 20 in Dubai last week before falling on Friday to Daniil Medvedev in the semi-finals.
Djokovic will be replaced in the field by Nikoloz Basilashvili, a brief statement said.On Friday, both the US Tennis Association and US Open organisers voiced support for Djokovic's request to be allowed to enter the United States.
"Novak Djokovic is one the greatest champions our sport has ever seen," the US Open wrote on its official Twitter feed.
"The USTA and US Open are hopeful that Novak is successful in his petition to enter the country, and that the fans will be able to see him back in action at Indian Wells and Miami."