Top seed Pete Sampras lost to Chris Woodruff in two sets in his opening match in the Kroger St Jude tournament in Memphis.
Woodruff took control of the match early in the second set.
Sampras, who won the tournament in 1996, failed to score a point until the third game of the set. Woodruff broke again in the seventh game for a 5-2 lead and served out the match.
"He was coming up with some great returns and seeing the ball great," said Sampras.
"I was kind of caught off guard."
Sampras, who entered the tournament after losing in the fourth round of the Australian Open, said he felt fine but needed to play more to sharpen his game following his 7-6 (7/4) 6-2 defeat by Woodruff.
"Unfortunately, the year’s been a little frustrating," he said.
It was Woodruff’s first win in four attempts over Sampras.
"I was just feeling it," said Woodruff.
"You get in these ideal performance states, and that’s what happened. This win is great. It does wonders for my confidence."