Harrison, who learned before the match that he was given a wild card entry into the U.S. Open, almost celebrated his trip to Flushing Meadows with a major upset battling the feisty Ferrer for two hours and 42 minutes on a blustery centre court.
Ferrer would have been prepared for a fight having needed five sets to stop Harrison in the second round of Wimbledon in 2011 and the young American did not disappoint the home crowd forcing the first set to a tiebreak before falling 7-5.
"Just wish I would have served a little better," said Harrison. "Obviously, I had some chances.
"I feel like my game is obviously right there on the brink of playing those top guys. That's kind of where you want it.
"Obviously, it would have been great to get a win today but I know that going in, if I compete the way I can and play the way I'm capable of, I'm going to be able to challenge just about anybody."
The match was the highlight during the morning session of a busy day at the Western and Southern Open, which brings together the top players from the ATP and WTA Tours in a joint event that for many will serve as their final tune-up to the August 26-September 9 U.S. Open.
Ninth seed Swiss Stanislas Wawrinka had smooth passage into the second round with a 6-3 6-4 win over Italy's Andreas Seppi while evergreen German 11th seed Tommy Haas advanced with a no-fuss 6-4 6-4 decision over South African Kevin Anderson.
Spain's Feliciano Lopez upset Japanese 10th seed Kei Nishikori 6-4 7-6 (4) while 15th seed Gilles Simon of France retired with a hip strain while trailing Canadian Vasek Pospisil 6-3 1-1.
Latvia's Ernests Gulbis, who knocked out Briton Andy Murray in the third round in Montreal, missed a chance at a rematch after a 7-5 6-3 loss to Russian Mikhail Youzhny.
Top-ranked American John Isner, a two-time winner this season, kept the home crowd happy with a steady 6-3 6-4 win over Germany's Florian Mayer.
(Editing by Frank Pingue)
