The Spanish world number one missed out on defending his title last June as he nursed his aching knees back home in Mallorca.
On the second day of the championships, he was back on a sun-soaked Centre Court and wasted little time in tormenting an opponent who he had once tipped as a 'future top 10 player'.
The 20-year-old Nishikori, on a comeback trail after missing most of the 2009 season with an elbow injury, had the audacity to break Nadal for 3-3 in the third set but his joy was short-lived.
Nadal powered to victory with an overhead smash on match point to set up a second round encounter with Dutchman Robin Haase.
In Image: Nadal gestures after his victory
Coverage: Wimbledon 2010