His theory will face a major test Wednesday when Facebook begins forcing its 100 million users to adapt to a redesigned Web site, whether they like the new look or not.
Since unveiling the makeover seven weeks ago, Facebook had left it up to users to decide whether they wanted to switch over. If they didn't like what they saw, the converts could just click on a link to switch back to the old format.
But that option will be taken away from all users by the end of the week, a shift that Zuckerberg already knows will alienate some of Facebook's audience and raise the risk of driving more traffic to rival social networks like MySpace and Bebo.
"Any change can be a big deal to our users because this is how they connect with their family and friends," Zuckerberg said. "So when you move things around, it can be perceived as being not a positive thing even when it's a positive change."
About 40 million users already have checked out the new design and about 30 million embraced it without reverting to the old look, Zuckerberg said.
But the seeds of an uprising already have been planted on Facebook's own site, where several groups and petitions have cropped up to protest the change.
"It's not that we don't want change, period, it's that we don't like these particular changes," said Scott Sanders, 19, an Austin Peay University student who started one of the petitions opposing the redesign. "You have to navigate more and you have to click more to get to personal profiles. It's too much effort to get to basic information."
Facebook's facelift separates users' personal profiles into different areas of the site and provides more tools that are meant to make it easier to share information and photos.
The revisions also shift various applications to the bottom of a person's home page and clears up more white space - a move that Sanders worries will lead to more intrusive advertising on the site, although Zuckerberg says that won't happen.
Hoping to minimize the sting of the anticipated backlash, Facebook announced the planned makeover in May and then waited until July to take the wraps off. The transition period since then was aimed at giving users time to make suggestions and get used to the change.
The gradual approach differed from how Zuckerberg and the rest of Facebook's unusually young management team have managed past revisions to the site.
In 2006, the Palo Alto-based startup infuriated thousands of users by introducing a tool called "news feeds" that automatically broadcast certain personal details. Last year, Facebook faced another revolt when it rolled out a tracking device, dubbed "Beacon," that tracked and shared information about users' shopping habits and other activities at other Web sites.
In both instances, Zuckerberg wound up apologizing for going too far and placated the protesters by giving more control over news feeds and Beacon. News feeds are now considered indispensable by many users, but Beacon still hasn't gained traction.
With Facebook's audience now roughly 10 times larger than when news feeds first came out two years ago, Zuckerberg understood he needed to do a better job preparing for changes.
"There is more weight on making things smooth when you are dealing with 100 million people," he said. "No one cared as much when a bunch of students from a few colleges were complaining about some changes to some Web site."
Although he is still hoping to persuade Zuckerberg to retreat from some of the changes included in the redesign, Sanders suspects resistance might be futile this time.
"I definitely won't stop using Facebook because it's still the best social network out there," said Sanders, who has been using the site for two years. "People will probably protest the changes in the beginning, but then they will just get used to them."