Second seed Murray shook off his post-Wimbledon cobwebs with a fighting 6-4, 7-6 (7/2) victory over Marcel Granollers. French Open champion Nadal too was in a menacing mode.
Eighth-seeded Del Potro, the 2009 U.S. Open champion, overcame a 3-0 deficit in the second-set tiebreaker to win, then took the third set in 31 minutes.
Nishikori missed the French Open last year because of an abdominal injury.
Jesse Levine was born in Ottawa and spent the first 13 years of his life growing up in Canada's capital city before moving with his family to Florida.
Americans Madison Keys and Jesse Levine have earned wildcard berths at the Australian Open by winning the U.S. Tennis Association playoff tournament.