Speaking during a closed-door testimony before the US House Oversight Committee, Gates admitted to having affairs with three women and said Epstein was aware of at least two of those relationships, media reports said.
He also acknowledged a separate affair with medical entrepreneur Alice Jacobs Nesselrodt.
While insisting the relationships were unrelated to his dealings with Epstein, Gates said the financier appeared to be gathering information that could potentially be used against him.
"These affairs had nothing to do with my interactions with Epstein, but they were painful for my family," Gates told lawmakers.
"Epstein was working to use information about my infidelities — in addition to many lies that he layered on top — to pressure me to re-engage with him."
'He contemplated blackmailing me'
Gates said Epstein never directly blackmailed him but acknowledged that emails reviewed during the congressional inquiry raised concerns about the financier's intentions.
"He never blackmailed me, but looking at these emails, it raises a serious probability that he contemplated blackmailing me," Gates said.
The billionaire philanthropist pointed to a 2013 email draft authored by Epstein that appeared to reference allegations involving Gates and his former adviser Boris Nikolic.
"Who knows if he ever sent it to Dr. Nikolic, but it looks like he's musing on using a mixture of facts and falsities as an effort, almost like a blackmail, to advance some goal," Gates told the panel.
Gates defends meetings with Epstein
Lawmakers also questioned Gates about the nature of his relationship with Epstein and why he continued to meet him despite knowing about his criminal conviction.
Gates reportedly said he met Epstein approximately 12 to 14 times and participated in two video calls with him over a four-year period.
According to Gates, the meetings centred on philanthropy and potential introductions to wealthy donors who could support charitable initiatives.
"I know he was convicted. I knew about that. I was willing to take a chance on meeting with him in a limited role," Gates said.
He added that the promised donor connections never materialised and described his continued association with Epstein as a mistake.
Gates rejects STD allegations
During the testimony, Gates was also asked about claims contained in Epstein-related documents suggesting he had concerns about a sexually transmitted infection following one of his affairs.
The Microsoft co-founder strongly denied the allegations.
"I never had an STD... I may have indicated some concern about whether I had an STD; I don't recall that. But I never had an STD. I never gave medicines to anyone covertly," Gates said.
Gates Foundation faces renewed scrutiny
The testimony comes amid renewed congressional scrutiny of Epstein's network and associates following the release of additional documents related to the disgraced financier.
The Gates Foundation has also launched an external review of its past interactions with Epstein after previously released emails revealed communication between Epstein and some foundation staff members.
Gates has repeatedly denied any connection to Epstein's criminal activities and maintains that their interactions were limited to discussions related to philanthropy.