Twitter mentioned Donald Trump nearly two times for every time Hillary Clinton was mentioned by the end of the debate, which the social media company said was the most tweeted debate ever.
In a series of tweets Sen. Elizabeth Warren of Massachusetts called Trump a "thin-skinned bully" and characterized his performance as that of a "man who was ranting & raving on stage."
Reince Priebus, chairman of the Republican National Committee, criticized Clinton during the debate and said she isn't trustworthy
The wordsmiths at Merriam-Webster joined in on the fun with a nod toward Trump's unique use of the word "bigly."
The word "stamina" became a buzzword later in the debate, spurring a flood of tweets.
And 400-pound hackers became another theme on social media.
Before the debate began, Dallas Mavericks owner Mark Cuban tweeted a photo of his front-row seat number.
Former President Bill Clinton tweeted that he is "looking forward to tonight's debate knowing that millions of Americans" will get to know the Hillary Clinton that he has known for more than 40 years.
Sen. Bernie Sanders emphasized that the candidates should focus on the issues and not treat the debate as an "entertainment show."
—CNBC's Michael Newberg contributed to this report.