The 36-year-old broke his right leg just 17 seconds into his fight with Uriah Hall. Weidman threw a leg kick which Hall blocked with his own leg, snapping Weidman's upon impact.
The middleweight fight was immediately halted with Hall declared the winner as Weidman was stretched off to a nearby Jacksonville hospital.
On Sunday, Weidman's wife Marivi posted a picture of the American fighter in his hospital bed after his surgery.
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"Well, that was horrible," she said. "Freak things happen in life and plans get crushed. It's been a long day but so happy to finally see this man of mine post surgery.
"My heart breaks for my husband because I know the work and dedication that he puts into his training everyday and the great man that he is, so I only want the best for him," she added.
"We were reminded this year how precious each day is and I am so thankful to be spending another day on earth next to my love even if it's in a hospital room far from home."
Coincidentally, Weidman was on the other end of almost the exact same injury about eight years ago.
Having claimed the UFC middleweight title from the legendary Anderson Silva, Weidman retained his belt against the Brazilian in the rematch in 2013 as Silva himself suffered a broken leg in the second round after Weidman blocked his leg kick.
Silva, who was sidelined for more than a year by his injury, took to social media to pay his respects to Weidman.
"My deepest and most sincere sentiments champ. Have faith," the 46-year-old -- who holds the record for the longest title reign in UFC history with 2,457 days -- wrote.
"I wish you a speedy recovery. In this moment, I wish you and your family light, love and knowledge. To the fans of the sport, please respect this moment of this incredible warrior and let's wish that he is 100 percent ... recovered soon."
Hall described hearing "a click" when Weidman's lower leg broke.
"I thought it was a slap, but I didn't feel the slap on my calf, so that's got to be his bone," he told the media in his post-fight press conference. "And when he landed, it clicked in. To be honest, it was just Anderson Silva when he landed. It was weird. It was so weird. I just pictured Anderson Silva."
Weidman had previously defeated Hall via a first-round knockout in 2010 before either fighter had made it to the UFC.
UFC 261 was the first full card of fights to be held in front of a full stadium of fans, with approximately 15,000 spectators crammed into the Veterans Memorial Arena in Jacksonville, Florida, to watch the action.