The freshman Duke center suffered a mild sprain to his right knee in the first minute of the game, his coach Mike Krzyzewski said, following North Carolina's 88-72 victory over the Blue Devils.
Williamson did not return to play as No. 1 Duke fell behind early and never recovered against No. 8 UNC.
Nike closed at $83.95 per share on Thursday, down from its previous closing price of $84.84.
"We are obviously concerned and want to wish Zion a speedy recovery," Nike said in a statement on Thursday. "The quality and performance of our products are of utmost importance. While this is an isolated occurrence, we are working to identify the issue."
Williamson was wearing the Nike PG 2.5 basketball shoe when he was injured, according to ESPN. The line of sneakers are a product of a collaboration between the world's largest sportswear company and six-time NBA All-Star Paul George, who plays for the Oklahoma City Thunder.
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Nike is Duke's exclusive supplier of uniforms, shoes and apparel under a 12-year contract that was extended in 2015 and has had an exclusive deal with the private university since 1992, ESPN reported.
"At this juncture, we are optimistic that while negative headlines might weigh upon Nike shares for a bit, any lasting damage to the company and its shares will prove minimal," Oppenheimer analyst Brian Nagel said in a note.
Williamson, who averaged 21.6 points a game, has been tipped as the "next Lebron James" and is expected to be selected first in the NBA draft this June.
Krzyzewski said it was unclear how long Williamson would be out because of the injury.
The game between the interstate rivals and two of college basketball's best teams was the marquee match so far in the season with tickets selling for thousands of dollars, according to multiple media reports.
Former President Barack Obama, director Spike Lee and star NFL running back Todd Gurley attended the game at Cameron Indoor Stadium, the home court of the Blue Devils.
TV cameras, focused on the concerned face of coach Krzyzewski in the foreground, caught Obama in the background, just behind the Duke bench. The 44th president and avid basketball fan Obama was pointing toward the floor and seemingly saying: "His shoe broke."
"Zion Williamson seems like an outstanding young man as well as an outstanding basketball player," Obama tweeted last Wednesday night. "Wishing him a speedy recovery."
Twitter blew up with criticism and colorful remarks against the world's biggest sports brand.
"Nike better give Zion the biggest shoe deal when he gets to the NBA.....Strong shoes that don't come apart," said one Twitter user.
A comedic Twitter feed, "Zion Williamson's shoe," was born in the wake of Wednesday night's injury. Its first tweet was a picture of Williamson's shoes, one of them blown apart, sitting under Duke's bench with the words, "Where is my dad?"
This is not the first time Nike has faced controversy over the craftsmanship of its sportswear.
In 2017, the Beaverton, Oregon-based company faced backlash when its NBA jerseys ripped apart after several incidents with basketball stars, including James.