Nole won the Best Male Tennis Player award at the 24th annual awards show at the Microsoft Theater on July 13 in Los Angeles.
The ESPY, short for Excellence in Sports Performance Yearly, honors sports achievement in the past calendar year.
Nole came out ahead over his hottest tennis rivals Roger Federer and Andy Murray.
He was also nominated for Best International Athlete (won by Cristiano Ronaldo).
Djokovic had previosly won the ESPY Best Male Tennis Player Award for achievements in 2011, 2012 and 2014.
The award for Best Female Tennis Player went to Serena Williams.