The world number one eased to a 6-3 6-3 victory over his opponent to overtake Rafael Nadal in the all-time list and win the Miami crown for the third consecutive year.
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It didn't get off to the best start for the Serb, however, as Nishikori hinted at a possible upset by breaking in the very first game.
However, Djokovic was soon back to the peerless form that had seen him win 21 straight Masters matches before this afternoon and, helped by some unforced errors from Nishikori, levelled things up at the first time of asking.
Back-to-back holds to love followed for Djokovic before he broke Nishikori again to move into a 4-2 lead, but the sixth seed was putting up a gallant fight and responded immediately with a second break of his own.
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The eighth game saw Djokovic turn down a challenge that Hawk-Eye showed would have been successful, but it didn't affect the Serb as he broke once again before serving out the set to love to clinch it 6-3.
More unforced errors from the Japanese saw him throw away the first game of the second set too as Djokovic gained an early break, and this time the double defending champion gave very little away on his own serve.
Nishikori also improved on his own serve, but Djokovic was able to earn a break point in the seventh game that he should have taken, only to miss a makeable winner.
It would not prove costly for the 11-time Grand Slam champion, though, as he held his own serve before breaking once more in the final game to take it 6-3 and clinch his sixth Miami title, drawing level with Andre Agassi.
It is also the seventh different location where Djokovic has won the title three times in a row, adding to his growing list of records as his dominance of the sport continues.