The royal is giving up his honors, such as the York's Duke, he has announced in a personal statement.
He has been under increasing attention over his associations with convicted criminal the financier, with demands for the monarchy to take action against him.
That now looks to have resulted in the prince deciding to willingly give up his honors and to surrender membership of the prestigious order.
In his message he said he continued to "vigorously dispute the accusations against me".
"In discussion with the King, and my direct and broader family, we have concluded the ongoing claims about me distract from the responsibilities of the monarch and the Royal Family," said a statement from Prince Andrew.
"I have decided, as I always have, to put my responsibility to my family and country first.
"I stand by my resolution five years ago to step back from official duties.
"With the monarch's approval, we believe I must now go a further step. I will therefore no longer employ my designation or the distinctions which have been conferred upon me. As I have said previously, I vigorously dispute the claims against me."
He has been involved in a number of issues, among them a legal case he settled with Virginia Giuffre, doubts about his finances and his connection with an accused foreign agent.
He will stay a prince - but will cease to be the Duke of York, a designation bestowed from his parent, the Queen Elizabeth II.
The prince had already stopped to be a "participating figure" and had lost the use of his HRH title and no longer appeared at state occasions. His role now will be even more lessened.
His former spouse will be known as Ferguson and no longer Duchess of York, but their children will carry on to have the designation of royal princess.
The royal has been under strong scrutiny over his links with disgraced financier Jeffrey Epstein, more recently involving doubts about when he had truly severed ties.
In his television appearance, he had said that he had ended all ties with the financier after they had been photographed together in NYC in late 2010.
But emails sent in early 2011 later surfaced implying that Andrew had confidentially remained in touch with Epstein, for example swapping a communication: "Remain connected and we'll have further interactions soon!"
There had been increasing frustration in Buckingham Palace at the issues that persisted to envelop the prince.
Soon a book released after death by Giuffre will be released which is expected to cast further attention on his association with Ms Giuffre and Jeffrey Epstein.
