Harris was hooked at three-quarter-time of Saturday night's season-opening two-point win over Geelong for what she called "precautionary" reasons, after hurting her troublesome left shoulder twice during the game.
The 27-year-old required treatment on her already heavily strapped shoulder, which was dislocated in a pre-season camp, after an innocuous incident in the first quarter.
After being cleared to return to play due to having "full strength and range of movement in her shoulder", Harris dislocated the joint when she received a strong tackle in the third term.
Coach Mick Stinear insisted after the game Melbourne "didn't see any risk" in playing Harris off a limited pre-season and were "comfortable" selecting her for the game.
But the Demons will now be without the athletic, high-marking tall for the remainder of their campaign after scans showed Harris had suffered a repeat anterior shoulder dislocation and required season-ending surgery.
"The extent of the damage unfortunately increases Tayla's risk of further dislocations and overall shoulder stability, and therefore the possibility of further structural impact, meaning she will require surgery," Melbourne's head of women's football Jessie Mulholland said.
"It's an incredibly disappointing outcome for Tayla, who had a strong block of full-contact training with her shoulder heading in, and was ready to attack her ninth season at the top level.
"Tayla is as resilient as they come, and we know she will tackle her recovery with the utmost professionalism and diligence, while helping her teammates be the best they can be.
"We will be there for Tayla every step of the way, and support her through this challenging period."
Harris had similar surgery on her right shoulder, and rehabilitated it successfully, in December.
She had been training down back during pre-season to add flexibility for the Demons, but will instead play a supportive role from the sidelines.
"I'm extremely disappointed to have my season cut short," Harris said.
"I now look forward to contributing in many ways off the field, and doing whatever I can to help us achieve our goal in 2024.
"I can't wait to be back on the field doing what I love in 2025."
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