Ivan Ljubicic was the first big name to fall at the 2006 US Open as he went down in straight sets to Spain's Feliciano Lopez in the first round.
Ljubicic reached a career best third in the world rankings this year
Lopez eased past the Croat, seeded third, 6-3 6-3 6-3 in one hour and 41 minutes on the Louis Armstrong Court.
"I didn't expect to lose this easy," said Ljubicic, who made 27 unforced errors. "He served extremely well. I never got to break point.
"He was returning my serves quite easily. It was really rough for me."
Lopez will play Switzerland's Marco Chuidinelli in the second round.
Former champion Andy Roddick opened his US Open campaign in impressive style, thrashing Florent Serra in one hour 19 minutes to reach the second round.
The 2003 winner continued the form that saw him win in Cincinnati last time out with a 6-2 6-1 6-3 win.
Roddick goes on to face Alberto Martin or Kristian Pless in round two.
"I felt great," said Roddick. "I only hit for a couple of minutes this morning because of the rain but am glad my form carried over from Cincinnati.
"I am playing comfortably right now, and I feel good."
Fellow American Mardy Fish was another early winner, beating Simon Greul of Germany 6-4 6-4 1-6 6-3.
Another American, 17-year-old Donald Young, made a promising start against 19-year-old Novak Djokovic in front of an enthusiastic crowd on Grandstand Court but the Serbian eventually came through 4-6 6-3 6-0 6-1.
France's Richard Gasquet, seeded 25, made a strong start with a 6-1 6-3 6-1 win over Phillip Simmonds of the US.
Wimbledon semi-finalist Marcos Baghdatis of Cyprus was also impressive in a comfortable 7-6 (7-1) 7-6 (9-7) 6-3 win over Germany's Alexander Waske.
Thailand's Paradorn Srichaphan had a characteristically epic battle in his opening match, battling past 24th seed Jose Acasuso of Argentina 6-3 3-6 7-6 (7-5) 6-7 (4-7) 6-3.