Zucker was instrumental in awarding The Tonight Show to O'Brien and moving former host Jay Leno to a primetime slot in 2009.
When ratings for both programmes declined, NBC executives sacked O'Brien and reinstalled Leno as The Tonight Show's presenter just six month after the initial switch.
Zucker accepted his role in O'Brien's exit from NBC after 17 years during a talk at the PromaxBDA's Conference, telling attendees he understands that his late-night scheduling decisions angered some viewers.
"I regret that we had to make the decisions. There were no winners out of that. A lot of people got hurt in that process. And that was incredibly unfortunate," he said. "Ultimately at the end of the day, it's my responsibility. Others were on the line to make the decision. But I signed off on it. So ultimately, it's my responsibility."
While Zucker conceded that moving Leno into a 10pm slot proved to be unpopular, he was reluctant to write the programming change off as a mistake.
He explained: "I don't regret necessarily what we tried by asking Jay to do 10 o'clock and Conan to do [The Tonight Show]. What I regret is neither show worked. That's what happened: Neither show worked. And then we had to make a decision about how to fix them."
O'Brien has described NBC's decision to fire him as host of The Tonight Show as a truly humanising moment.
Zucker himself parted ways with NBC last September after the channel's merger with Comcast was complete.
He has signed to executive produce Katie Couric's upcoming talkshow for ABC, which is to debut in the fall of 2012.
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Watch Conan O'Brien's Tonight Show farewell below: