Djokovic dropped serve in the first game against Nishikori but it was pretty much one-way traffic after that as he outclassed the sixth seed in all facets of the game on the hardcourt at Key Biscayne.
The 28-year-old Serb took 85 minutes to join American Andre Agassi as a six-time Miami Open winner.
Djokovic said his first Miami win in 2007 paved the way for a career that now includes 63 ATP titles.
"It gave me a lot of confidence, a lot of self belief that I can finally win these big tournaments, finally beat the top players," he said in a courtside interview.
"Every year I come back to this tournament I get goose bumps from those days. I was still 19 years old and making my way to the top."
He collected $1,028,300 on Sunday, becoming the sport's all-time leading money-winner with career earnings approaching $100 million.
It was his fourth consecutive championship, and a record 28th overall, in the Masters 1000, a series of nine tournaments considered the most prestigious other than the four grand slams.
"First set was a real battle, but towards the end of the first set I started serving better... which means a lot in matches like this against top players," he said of his latest victory.
It was Djokovic's fourth title of 2016, following victories at the Australian Open, Qatar and Indian Wells.
His only blemish on an otherwise perfect record so far this year came in Dubai in February, when he retired during a quarter-final with an eye infection.
Djokovic will fly home on Monday to Monte Carlo, where he will begin his clay court season next week.
"I have plenty of energy and lots of motivation for the beginning of the clay court season that ends up, hopefully, with a crown in Paris (in June)," he said.
"That’s obviously one of the top goals each year, but I’m not the only one that wants to win that big trophy. There are many big events prior to that so I’m hoping I can build my form."
(Reporting by Andrew Both in Cary, North Carolina; Editing by Ken Ferris)
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