But Trump never openly insulted Clinton, never called her "Crooked Hillary", nor did he cross the stage at any point, as a former senate opponent famously did with Clinton in 2000 - a move that was seen as physically intimidating towards a female candidate.
Despite that, gender and sexism did feature prominently during several exchanges in the debate, and in the initial feedback on the candidates' performance on social media.
Trump was the first to interrupt Clinton early in the debate, and he did so almost once per minute in the first 25 minutes according to a tally by Vox.
"Wrong, wrong, wrong," he interjected during one of her responses, and at one point just blurted "not."
In total, Vox says Clinton interrupted Trump 17 times, while he spoke over her 51 times.
"A male candidate can't look like he's bullying a woman," says Jennifer Lawless, a professor at the School of Public Affairs at American University. "Whether it be hand waving or sighing or rolling his eyes, that can be perceived as far more condescending because she's a woman."
For her part, Clinton seemed resolute about not allowing Trump to cut her off.
"It's almost as if women are used to men constantly talking over them!" one observer tweeted.
2. Name power play
Trump stopped himself the first time he addressed Clinton by her name.
"In all fairness to Secretary Clinton - is that OK? I want you to be very happy," he said.
Clinton, however, consistently referred to her opponent as "Donald", a movedescribed by Slate as a "power move".
"Hillary Clinton referred to @realDonaldTrump by first name 22 times. Trying to get under skin?" the political blog Presidential Gender Watch tweeted, attributing it to PBS Newshour host Gwen Ifill.
At one point, moderator Lester Holt directly asked Trump about his previous comments that Clinton didn't have a "presidential look", a comment that has been derided as blatantly sexist.
Rather than try to parse his words, Trump simply restated the comment.
"She doesn't have the look. She doesn't have the stamina. You need tremendous stamina," he said. "I don't believe Hillary has the stamina."
Kelly Dittmar, a scholar with the Center for American Women and Politics, accurately predicted that Donald Trump might bring up the issue of Hillary Clinton's "stamina and strength". Dittmar describes this type of attack as a coded way of highlighting gender.
"There's a perception of feminine vulnerability and weakness that he cues," says Dittmar. "He's the strongest, toughest, most manliest candidate and she is the opposite."
Clinton shot back that, "As soon as he travels to 112 countries and negotiates a trade deal and a cease fire or even spends 11 hours testifying in front of a congressional committee, he can talk to me about stamina."
Trump also did not distance himself from comments he has made in the past about Rosie O'Donnell's appearance. When Clinton mentioned Alicia Machado, the Miss Universe winner he once had work out in front of the press after she gained weight, Trump seemed to deflect by making an oblique reference to former president Bill Clinton's past infidelities.
"I was going to say something extremely rough to Hillary and her family, but I said I can't do it," he said.
4. The smile
In the past, Clinton has been criticised for not smiling enough, seen as another classic case of gender bias against female politicians.
"[Trump] doesn't smile a great deal in these debates and he can get away with that as a guy," says Leonie Huddy, a professor of political science at Stony Brook University. "A woman can't."
This time around, however, smiling too much seems to have been a point of attack.
"Who told Hillary Clinton to keep smiling like she's at her granddaughter's birthday party?" tweeted David Frum, senior editor at The Atlantic.
"Looking manic, condescending," wrote another Twitter user. Others shared pictures of Clinton as the joker.
Another tweet from Meet the Press attributed to host Chuck Todd was met with dozens of negative responses, after Todd said that Trump seemed unprepared while Clinton was "over-prepared".
"No one hates the smartest girl in the room more than the dumbest guy in the room," wrote one.