The out-of-sorts Romanian, who called for medical attention after losing the first set, went down 6-3, 6-1 to American Shelby Rogers on day one in hot conditions on Rod Laver Arena.
Halep was playing the first match of the tournament on the centre court, and she became the first major casualty. It was a case of deja vu for the right-hander, who was sent packing at the same stage last year by Chinese qualifier Zhang Shuai.
The 25-year-old is one of the fastest movers on court but she was missing her usual zip against the American, who reached the French Open quarter-finals last year.
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“I had knee pains,” she said, adding that she first felt the tendon problem in October at the WTA Finals in Singapore. “For me, in the second set, was difficult to move anymore, but she deserved to win. She was aggressive, and she hit very strong.”
Asked about crashing out in the first round once again, she replied: “I'm a bit frustrated, but you cannot change much.
“I'm okay. Just looking ahead. It happens, and I just want to be well with the knee. And then I will think about the game.”
Rogers, in only her second Australian Open appearance, was ecstatic at claiming such a big scalp, having missed last year's tournament to focus on a lower-level ITF Tour event in Florida after injury problems.
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“It's pretty incredible, I played really well today,” said the 24-year-old, ranked 52 in the world. “There are no easy matches at this level so I am happy to get through and I take a lot of confidence from today.”
She added that making the last eight at Roland Garros had given her the belief that she can beat the top players.
“The biggest thing I took away from that was just that I can compete with the top players in the world and I'm good enough,” she said. “So I have definitely carried that away from the French Open and just been enjoying it a little bit. There has been a lot of positive feedback, which has been nice. I'm just trying to keep that going.”
Playing the first match of the tournament on centre court, Rogers held serve first up when Halep sent a backhand wide as both players adjusted to the conditions.
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As sweat quickly started dripping off them, it went with serve to 2-2 in a close-fought contest as Halep was forced to save two break points to stay at level pegging.
Rogers, coming off a run to the quarter-finals at the Hobart International, finally got the break in the sixth game to lead 4-2 when Halep smashed a volley into the net.
The sluggish Romanian saved two set points on her next service game but Rogers wasn't to be denied and she wrapped up the set 6-3 in a gruelling 46 minutes.
The usually tenacious Halep was clearly struggling and she called for the trainer at the changeover.
But a confident Rogers broke in the third game of the second set to go 2-1 ahead before quickly reeling off the last four games.
Rogers' reward is a second-round clash against either Australian qualifier Ashleigh Barty or Germany's Annika Beck.
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