Al Franken, who has served as senator to Minnesota since 2009, quickly issued a statement apologising to sports broadcaster and former model Leeann Tweeden, who said the inappropriate behavior occurred when they were both on a tour entertaining US troops deployed in Afghanistan.
Tweeden said Mr Franken, at the time a prominent comedian, writer and liberal talk radio host who had risen to fame on the satirical show Saturday Night Live, had written a sketch in which he was meant to kiss her on stage in front of the troops.
During rehearsals for the comedy turn, Tweeden said Mr Franken "came at me, put his hand on the back of my head, mashed his lips against mine and aggressively stuck his tongue in my mouth."
The accusation came amid a surge of claims of sexual harassment leveled at senior male figures in the entertainment, media and political establishments, after Hollywood mogul Harvey Weinstein was denounced for decades of sexual abuse.
Tweeden said nobody witnessed the incident, and that she immediately pushed Mr Franken away and went to wash out her mouth, feeling "disgusted and violated."
On the long flight home aboard a military cargo plane, Tweeden said that while was asleep in body armor and helmet, Mr Franken posed for a photo in which he appeared to grope her breasts. She only discovered the image after she returned home and was sent pictures of the trip.
"I felt violated all over again. Embarrassed. Belittled. Humiliated," she wrote on the website of KABC radio in Los Angeles, where she hosts a show. "How dare anyone grab my breasts like this and think it's funny?"
Franken, who was re-elected to the Senate in 2014, issued a statement in response to the charges.
"I certainly don't remember the rehearsal for the skit in the same way, but I send my sincerest apologies to Leeann," he said. "As to the photo, it was clearly intended to be funny but wasn't. I shouldn't have done it."
Mitch McConnell, the Republican majority leader in the Senate, called for the chamber's Ethics Committee to review the matter, "as with all credible allegations of sexual harassment or assault.
"Regardless of party, harassment and assault are completely unacceptable - in the workplace or anywhere else."
The top Democrat in the Senate, Chuck Schumer, joined in calling for the committee to " fully investigate this troubling incident," saying in a statement that "sexual harassment is never acceptable and must not be tolerated."
