The 31-year-old Spaniard won 6-3 6-2Â in 94 minutesÂ to claim a record-extending 11th triumph at the clay-court event.
Nadal has won 36 straight sets on his favoured surface after proving too strong for world number 36 Nishikori.
He had to win the Masters 1000 tournament to prevent Roger Federer overtaking him in the rankings.
“It’s always special for me to be back here, having this trophy. It’s one of the most important events of the year for me,” said Nadal.
He was pushed by Nishikori at the start of the first set and fell a break down, but the 16-time grand slam champion hit back to take the openerÂ in 56 minutes.
And despite this week representing only his second tournament outing after sustaining a hip injury at theÂ Australian Open,Â Nadal won five straight games in the second set en route to his record 31st Masters title.
“I want to thank all my team and my family. We had some tough moments during the past five months after a couple of injuries in a row,” added Nadal.
Nadal withdrew from the Mexican Open, Indian Wells Masters and Miami Open because of the hip problem before returning at the start of the month for Spain’s Davis Cup quarter-final against Germany.
Former world number four Nishikori only returned from a four-month absence with a right wrist injury in January.
“I want to congratulate Kei (Nishikori) for a great week. It’s always difficult to be back from injury and I’m happy to see you again playing well,” said Nadal.