World number 1 has been disqualified from the US Open for accidentally hitting a ball at a line judge in his fourth-round match.
Djokovic, 33, hit a ball behind him in frustration after losing serve to trail 6-5 against Spain's Pablo Carreno Busta.
After a lengthy discussion, he was defaulted by tournament officials.
The ball hit a female line judge, who dropped to her knees at the back of the court and reached for her neck.
Djokovic was aiming for an 18th Grand Slam triumph to move closer to rivals Rafael Nadal and Roger Federer, who are not playing in New York.
The star did not attend the post-match press conference, but in a post on his Instagram following the incident he said he was "so sorry".
"This whole situation has left me really sad and empty," he said.
"I checked on the lines person and the tournament told me that thank God she is feeling ok.
"I'm extremely sorry to have caused her such stress. So unintended. So wrong."
The player said he would turn the incident into a "lesson" for his "growth and evolution as a player and human being".
Djokovic was the favourite to win the men's singles title at the US Open, which is being played behind closed doors and is the first Grand Slam to take place since the beginning of the coronavirus pandemic.
In a statement, US Open officials said he will lose all ranking points earned and will also be fined the prize money he has won.
"In accordance with the Grand Slam rulebook, following his actions of intentionally hitting a ball dangerously or recklessly within the court or hitting a ball with negligent disregard of the consequences, the tournament referee defaulted Novak Djokovic from the 2020 US Open," the state said.
Tim Henman, who was disqualified from Wimbledon 25 years ago for accidentally hitting a ball girl with a ball during a doubles match, said there was "no doubt that it's the right decision".
Speaking on Amazon Prime, he said: "It's amazing for me to talk about this because it happened to me at Wimbledon in 1995. It was that moment of frustration, hit the ball away when I wasn't looking and I hit a ball girl in the ear."
Djokovic will face another fine for not doing the press conference, after he was seen getting into a car and leaving the site.
Djokovic's exit means there will be a new male Grand Slam champion for the first time since Marin Cilic won at Flushing Meadows in 2014.
Second seed Dominic Thiem, who has reached Grand Slam finals three times without a win, is now the highest-ranked player remaining.