"I know you said you want the investigation to continue," Stephanopoulos told Biden, referring to a probe by New York's attorney general into allegations Cuomo had harassed several women. "If the investigation confirms the claims of the women, should he resign?"
"Yes," the president replied. "I think he'll probably end up being prosecuted, too."
Seven accusers have in recent weeks raised allegations against the Democratic governor, and one claim he groped a woman was referred to police in Albany, N.Y. A number of top Democrats from New York, including Senate Majority Leader Chuck Schumer and Sen. Kirsten Gillibrand, have called on Cuomo to step down.
Cuomo has denied the allegations.
Biden has so far stopped short of backing an immediate end to Cuomo's governorship.
"There should be an investigation to determine whether what she says is true," Biden told Stephanopoulos during a wide-ranging interview in Darby, Pennsylvania. "That's what's going on now."
He added: "There could be a criminal prosecution that is attached to it. I just don't know."
"Senator Schumer, Senator Gillibrand, the majority of the congressional delegation don't think he can be an effective governor right now," Stephanopoulos asked. "Can he serve effectively?"
"Well, that's a judgment for them to make," the president said.
Biden said "a woman should be presumed telling the truth and should not be scapegoated and become victimized by her coming forward."
"Takes a lot of courage to come forward," the president said. "So, the presumption is they should be taken seriously. And it should be investigated. And that's what's underway now."
Biden's comments Tuesday went a step further than his only other public remarks on the allegations against the governor.
On Sunday, asked by ABC News during a brief exchange about whether Cuomo should resign, Biden had said, "I think the investigation is underway and we should see what it brings us.”
The president visited the Philadelphia suburbs Tuesday to promote the $1.9 trillion COVID-19 relief bill he signed into law last week.
Watch more of the interview with President Joe Biden on ABC's "Good Morning America" on Wednesday, March 17, at 7 a.m. EDT.