The in-person debate, to take place at Belmont University in Nashville, Tenn., will be moderated by NBC White House correspondent Kristen Welker.
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The debate will begin at 9 p.m. EST and run for approximately 90 minutes without commercial interruptions.
Welker has picked six topics to ask candidates about, although the Trump campaign requested earlier this week that the debate questions focus more on foreign policy.
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Each candidate is afforded two uninterrupted minutes to speak at the beginning of each 15-minute segment, and the microphone for the candidate who is not speaking during that time will be muted. Both candidates' mics will be open for the rest of each segment, allowing candidates to interject as they go back and forth on the issues.
"We haven't changed any rules, we have just put in a system where when one is talking just for that two-minute period, the other can't interfere," debate commission co-chair Frank Fahrenkopf told "The Story" on Wednesday.
"They both will get a full two minutes in each of those segments to talk [and] the rest of the time, there is no muting, no buttons to push, they will be able to go at each other the way they want to," Fahrenkopf continued.
Fox News' Tyler Olson contributed to this report.