During a engagement to Lichfield Cathedral on Monday, the King was confronted by a man who questioned him about his brother's connections with convicted sex offender Epstein.
The man asked how long the monarch had been known about his brother's relationship with Epstein, and also raised doubts about whether he had asked the police to "conceal" for Andrew.
Despite the heckling, there were crowds of fans and cheers for the monarch, who was visiting the region for an event.
Prince Andrew's links with Jeffrey Epstein have been under intense scrutiny in the past few weeks. The prince, who gave up his royal duties earlier this month, has strongly denied any misconduct.
"For how long have you been aware about Prince Andrew and Epstein? Did you request the authorities to cover up for Andrew?"
The monarch ignored the questions but continued greeting supporters, some of whom chanted "God Save The King". One supporter can be heard requesting him for a embrace.
A female bystander outside the venue was also observed telling the protester to "leave" and to "shut up".
The scandal over the Duke of York's links to Epstein has been revived by sexual abuse allegations detailed in Virginia Giuffre's recently released memoir.
In the publication, Ms Giuffre claims she had sexual encounters with the prince on multiple times, including once with Epstein and "eight other young girls"
Andrew, who agreed to a financial settlement with the plaintiff in 2022, has repeatedly denied any misconduct. In 2019, he told BBC Newsnight he did not remember meeting her "at all", and that they "did not have any sort of intimate relations."
But in recent times, fresh questions have been raised about how he is able to fund his way of life despite not being a working royal.
The disclosure that he has only ever paid a token annual rent on his Royal Lodge has heightened the scrutiny over his living arrangements - even though he made large payments up front, including for improvements.
The Liberal Democrats said he should be called in front of MPs to give evidence about his rental agreement of his residence.
But last week, the authorities declined to give MPs time to discuss the prince's status or his residence, despite growing pressure for scrutiny.
Buckingham Palace has not commented on whether Prince Andrew might move out of his home - or where he might go.
Elena Marchetti is a technology journalist with a passion for demystifying complex topics. She has been covering tech trends for over a decade.