In a bizarre twist, the candidates took the stage to an empty auditorium, after broadcaster RayCom decided at the last minute to close the event off to the public.
As the event was set to begin, student protesters surrounded the auditorium as police held them back with pepper spray and tasers.
Student journalist Nick Reimann from Loyola University of New Orleans said he saw "at least 50, maybe 100" protesters at one of the building's entrances.
"Guys were jumping all over the place, just mace, pepper spray," he said. "I literally can still taste the pepper spray."
The university announced via Twitter that there had been no arrests made, but that two individuals were briefly apprehended after trying to breach the door.
"I think David Duke was a catalyst for a broader conversation about how their institution and our city at large sort of view people of color."
The protests were led by student activist group Socially Engaged Dillard University Students, who sent a letter to university administrators after the announcement of Duke's participation in the debate. "His presence on our campus is not welcome," it read.
In response to the growing student and community backlash against Duke's presence, the university released a statement Wednesday saying that it "stands by its contractual obligation to host the debate. We also reiterate that the University has had no input with regard to the criteria of selection or issuing of invitations to candidates for this event."
"Understanding the electoral process," the statement read, "including the elements that we may not agree with, is vital to the success of our American democracy."
After the protests, the university tweeted that it respects students' rights to protest, and that its primary focus would be the safety of the student body.
Inside Georges Auditorium, despite moderator John Snell's efforts at keeping the conversation away from Duke, saying it would be "an enormous disservice" to voters to focus on him, the candidates continued to reference him.
After Democratic candidate Campbell Foster was accused of having a friendship with Duke, he responded, "I have nothing in common with David Duke, other than we're probably breathing."
Republican candidate John Fleming said of Duke, "It must be terrible to wake up in the morning with that much hate in your heart."