In the video posted on Twitter, the blonde-haired woman can be seen standing on stage in front of Affion and another woman.
Affion, 47, asks her to tell him what she wants to know.
The other woman then steps off the stage and the blonde-haired woman tries to explain herself to Affion and the audience.
She says: "I'm a woman. And I'm married to a man. But you've insulted a lot of people tonight."
Affion says: "How? How am I insulting people by talking about sexual matters between adults?"
The comedian and actor from North Carolina, US receives a round of cheers from the audience.
"I'm talking about consenting adults here," he says.
"I have sex. I have sex with women.
"So me being up here describing my life is insulting to you?"
Affion then stretches his arm out to the woman following his question.
The woman has no microphone but says something inaudible in response.
Affion says: "How do you speak for the whole crowd and tell me I'm insulting them?"
He then turns to the audience to ask whether anyone else was insulted.
People are jeering but the woman stays on stage and also tries to attract supporters from the audience to her side.
Affion says: "Is anybody insulted?
"Sounds like a resounding 'yes' over here."
Two venue staff then approach the stage and encourage the woman to go back into the audience.
She steps down the front to jeers of 'Karen' from the crowd.
Affion says after she's left: "See white people can do whatever the f*** they want - storm the Capitol or storm my goddamn stage."
Affion started his career in 1996 when he appeared in the HBO-aired series Def Comedy Jam.
Turning to more acting roles, he featured alongside big names like Samuel L Jackson, Kevin Hart, and Adam Sandler.
Affion then produced his own sketch comedy show produced by rapper and actor Jamie Foxx called In The Flow With Affion Crockett.
Words: Charlie Metcalfe
Featured Image Credit: Twitter/@davenewworld_2