The Serb collected his fifth title of 2016 after winning the Qatar Open, Indian Wells, Miami Open and Australian Open, in which he also defeated Murray in the final.
The Scot, who also lost second place in the world rankings to Roger Federer, knocked out crowd favourite Rafael Nadal in the semi-finals but Djokovic proved a more formidable opponent, breaking him three times in the opening set.
Murray hit back in the second but had no answer in the third as Djokovic repeated his 2011 Madrid Open triumph.
“I started very well and played terrific tennis in the first set,” said Djokovic.
“There were a couple of close games in the second set ... and I made some unforced errors and double faults in the game when I dropped my serve. So I fought...very hard.”