The British number two was playing on a show court at his home grand slam for the first time, but slipped to a 6-4 6-4 6-0 defeat.
Apart from the opening half of the first set, Norrie was unable to compete with the Japanese eighth seed as his best Wimbledon run came to an end.
Nishikori looked close to his best as he had Norrie scrambling on both wings and he now meets Steve Johnson in the third round on Saturday.
It might have been different had Norrie been able to take advantage of an early break of Nishikori's serve, but serving for a 5-2 lead he put in a sloppy game.
Nishikori, a quarter-finalist last year, went on to win four games in a row and take the opener in 40 minutes.
There were three successive break of serves at the start of the second set, but unfortunately for the home player two of them went to Nishikori and he eased into a 2-0 lead.
Norrie's spirit had been well and truly broken by the time Nishikori broke in the opening game of the third set.
An unscheduled stoppage, where play was delayed for five minutes while an unwell spectator on the sweltering Centre Court was attended too, could not alter the momentum, as the heat coming from the other side of the net was too hot for Norrie to handle.
When the game resumed at 2-0 in the final set, Nishikori rattled through it to seal an impressive win.
Join our new commenting forum
Join thought-provoking conversations, follow other Independent readers and see their replies