Despite the disappointing 4-6, 7-6, 6-4 defeat, the 30-year-old said she was confident she still had a lot of tennis left to play.
"I definitely feel like I'll be back next year," Williams said. "This is what I do and I feel like I played great tennis even with minimal preparation."
Williams, who was aching to add a third US crown nine years after collecting her last, had not played a match since Wimbledon due to a knee injury but yet was agonisingly close to reaching the final.
After winning the first set 6-4 while losing only five points on serve, the seven-times grand slam winner reached a second-set tiebreaker against the Belgian before she suddenly wobbled on serve to start a slide to defeat.
Back-to-back double faults handed second seed Clijsters a big edge in the tiebreak and Williams never recovered after losing all four points on her serve to drop the decider 7-2.
"Obviously in the tiebreak I wasn't able to play as well as I wanted," the American third seed said. "I had too many errors, and she played some good tennis. I just wish I could have played the bigger points a little better."
Williams said the wind bothered her during her serves in the tiebreaker, but added: "Regardless, I've got to get it in and start the point.
"It's extremely disappointing not to be able to win this match today."
After winning her previous five matches in straight sets, and carrying the Williams family banner alone in the absence of her injured younger sister Serena, Venus had hoped this might be her return to Flushing Meadows glory.
"I may have lost the match, but that's just this match. There will be others," she said.
"I feel like as long as I'm striking the ball well, I'm gonna keep playing. At this point I'm striking the ball well, so there is no end in sight at the moment."
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