The world number one matched Andre Agassi’s Miami tally with a 6-3, 6-3 triumph in one hour and 26 minutes.
Djokovic, 28, also moves ahead of Rafael Nadal with a record 28 Masters tournament wins in his career.
“It’s quite amazing,” said the Serb. “I’m very thrilled about it and hopefully I can make many more records.”
He also becomes the first man to win the Indian Wells-Miami double three years in a row, and surpasses Roger Federer as the ATP’s leading prize money winner on $98.2m (£69m).
‘It’s tough to find his weakness’
Japan’s Nishikori broke serve in the opening game but was broken straight back, and after a scrappy start to the match Djokovic took charge from 4-3.
He won four games in a row to move a break up in the second set and broke for a fifth time to win the match.
“I thought he started very well, breaking my serve in the first game and coming up with some aggressive play,” said Djokovic.
“I needed to answer right back, which I did in the following game – that helped me mentally.”
Nishikori, 26, said: “It’s tough to find his weakness, honestly. The biggest thing is he has great defence and it’s tough to open up the space.
Djokovic has only one loss to his name in 29 matches this year – and that was a retirement with an eye infection in Dubai.
With 11 Grand Slam titles, the Serb is already among the very best ever to have played the game – and catching Federer’s record tally of 17 majors is in his thoughts.
“Of course it is in the back of my mind somewhere but I don’t have that as a main motivation, because it can present some kind of distraction that I don’t need,” he said.
The next few months could go a long way to making his case as he gets the chance to land the two biggest titles to have eluded him – the French Open and Olympic gold.
“I don’t feel too exhausted,” he said. “I don’t think I will have any difficulty to make the transition to the clay courts quickly. Let’s see what happens.
“Clay courts are the most physically demanding surface, so also looking at the big picture, the French Open is the biggest goal that I have on the clay courts. I’ll try to adjust to that tournament as well.”