Murray battled past Djokovic 6-4, 7-5, 6-4, ending Britain's 77-year drought in claiming the country's first All England Club crown since Fred Perry won in 1936.
Murray pulled off the feat after falling to Roger Federer in last year's final.
In reaching his second Wimbledon final, he joined just Perry and Bunny Austin as the only British men to reach multiple finals since 1922.
It was the second career Grand Slam for Murray, who also defeated the Serbian superstar at the 2012 U.S. Open. He fell to Djokovic in the finals of the 2011 Australian Open title match.
"I understand how much everyone wanted to see a British winner at Wimbledon, so I hope you enjoyed it," Murray told the crowd after the match. "I tried my best."
Djokovic, meanwhile, came up short in his bid for a seventh Grand Slam title, falling to 11-8 all-time against the 6-foot-3 Scotland native and 37-20 in title matches.
Murray gained control of the match by taking the second set after falling behind 4-1, winning six of the next seven games.
He turned back a Djokovic rally in the third set, notching wins in the final four games to take the title, improving to 28-14 all-time in finals.