Djokovic joins world number one Andy Murray on the sidelines for the elite hard court tournament.
"I apologize to my fans and ppl who purchased tickets to watch me play live at @MiamiOpen. Sadly, I'm injured and won't be able to compete," the Serb star said on Twitter.
Tournament organizers confirmed in their statement that Djokovic was battling an elbow problem.
"Novak Djokovic has been forced to withdraw due to an elbow injury," officials said. "We wish a quick recovery to our champion."
Djokovic joins world number one Andy Murray on the sidelines for the elite hard court tournament. Murray pulled out Saturday with an elbow injury.
Even as Murray was announcing his withdrawal on Saturday there were reports that Djokovic was seeing a doctor in Monte Carlo about elbow trouble after falling in the fourth round to 16th-ranked Australian Nick Kyrgios in the Indian Wells Masters.
It Kyrgios's second victory in as many weeks over Djokovic, after an upset triumph in the quarter-finals at Acapulco.
Not only are the world's top two men missing from the Miami event, the biggest name in the women's game, Serena Williams, will miss the Florida tournament with the knee trouble that also caused her to opt out of Indian Wells.
The tournament will, however, have the women's world number one, with Germany's Angelique Kerber posed to return to the summit on Monday despite a fourth-round exit at Indian Wells because of Williams's inactivity.
Kyrgios's triumph over Djokovic ended the Serb's 19-match winning streak at Indian Wells, where he had won the last three titles to go with those he took in 2008 and 2011.
Djokovic's withdrawal from Miami is just the latest setback for a player who endured a drop in form after completing the career Grand Slam with a long-sought French Open victory last year.
He relinquished his Wimbledon and US Open titles and was shocked in the first round of the Rio de Janeiro Olympics last year by Juan Martin del Potro, losing his world number one ranking to Murray along the way.
Although he opened 2017 on a promising note with a title in Doha, he slumped to a second-round exit at the Australian Open, and didn't play again until Acapulco.