Eighth seed Fish was less happy to play in the scorching afternoon heat, complaining about the timeouts that Colombian opponent Alejandro Falla took for treating cramps before sealing a 7-6 (7-4) 6-3 7-6 (8-6) victory.
Meanwhile Federer was never seriously troubled as he earned a clash with either American 23rd seed Mardy Fish or Gilles Simon, the French 16th seed.
U.S. hopes were boosted by a superb win by 23rd seed Mardy Fish over Russian Nikolay Davydenko.
Spadea's fellow American, eighth-seed Mardy Fish dropped a set against Lee Hyung-taik of South Korea before winning 6-4 3-6 6-1.
Monaco celebrated his 28th birthday with a comprehensive 6-1 6-3 defeat of U.S. No. 1 and eighth seed Mardy Fish .
Fifth seed Mardy Fish maintained the form he showed last week by moving into the second round with a comfortable win over Julien Benneteau.
American ninth seed Mardy Fish also exited after being hampered by the abdominal problem which forced him to forfeit in the L.A. quarterfinals.
Another home player in fine form was British number two James Ward , who took 10th seed Mardy Fish all the way in a gruelling five-set match.
But 19th seed Mardy Fish , runner-up to Roger Federer in Cincinnati , recovered from a mid-match wobble to overcome Jan Hajek 6-0 3-6 4-6 6-0 6-1 and 23rd seed Feliciano Lopez beat Santiago Giraldo in straight sets.
The Flushing Meadows crowd had much to cheer about on Louis Armstrong as 19th seed Mardy Fish , a recent finalist at the Cincinnati Masters, fired 14 aces on his way to an impressive 7-5 6-0 6-2 win over Uruguay's Pablo Cuevas.
BBC: Roger Federer wins at US Open as Davydenko & Cilic lose
World No. 1 Roger Federer begins his bid for a record-equaling 17th Masters 1000 tournament victory against Ecuador's Nicolas Lapentti on Saturday, while third seed and defending champion Andy Murray takes on American Mardy Fish.
CNN: Djokovic dumped out in Miami; Clijsters and Henin progress
Seventh seed Marin Cilic edged out Marcos Baghdatis 6-3 6-4 while Mardy Fish -- who knocked out holder Andy Murray -- continued his fine form with a 7-5 6-3 win over Feliciano Lopez.
In other first-round matches, 2006 Australian Open finalist Marcos Baghdatis of Cyprus beat American Mardy Fish 7-5 7-5 to earn a second round clash against fourth-seed Tomas Berdych, who beat Australian qualifier Nick Lindahl in straight sets.
Top seed Nadal, the 2005 champion, next faces Richard Gasquet after the Frenchman overcame 23 aces by American Mardy Fish to win 6-7 (7-3) 6-4 6-3.
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