Within two hours of the debate ending, the Democratic Party had set up various ways to capitalise on the online merriment, including tweeting a photo of presidential nominee Joe Biden saying, "Pitch in $5 to help this campaign fly."
Two hours later the Biden website was also selling branded $US10 ($15) flyswatters with the phrase "truth over flies". A few hours later, a spokesperson for Biden's campaign announced they'd sold all 35,000 of the flyswatters.
On Twitter, the hashtag #flygate was trending throughout the evening, as were the words "fly", "the fly" and "flies".
Within minutes of the debate ending, a quick-fingered web user had already set up a Twitter account claiming to be the fly itself.
The account, FlyOnMikePence, posted a number of tweets and gathered almost 7000 followers, joking it needed to quarantine after landing on Pence's hair. It also said it chose Pence because flies love things that are "dead on the inside".
Shortly after the debate ended, Biden shared a photo of himself with a flyswatter that's attracted more than 870,000 likes.
The Democratic Party also quickly set up a voter registration site under the flywillvote.com URL.
Harris and Pence sat at distance and were separated by two plexiglass barriers during the VP debate in Salt Lake City, Utah.
The debate drew considerably more attention than previous vice presidential debates. Biden and President Donald Trump, both in their 70s, are two of the oldest candidates in the history of the US elections.
If either Biden or Trump were to become unable to serve, Harris or Pence would take over the role of president.