On the 14 April 1659 she married Roger Palmer (later 1st Earl of Castlemaine) against his family's wishes; his father predicted that she would make him one of the most miserable men in the world. Barbara already had three lovers before she married Roger. One of them was Philip Stanhope, whom she gave her virginty to. Just a year after they were married, she became the mistress of King Charles II.
The two separated in 1662, following the birth of her first son. They remained married until the death of Castlemaine, who predeceased Villiers, but it has been claimed that he did not father any of his wife's children. Although, he did thought that her first child/eldest daughter was his.
Barbara Villiers became King Charles's mistress in 1660, while still married to Palmer, and while Charles was still in exile at The Hague. The Palmers had joined the ambitious group of supplicants who sailed for Brussels at the end of 1659. As a reward for her services, the King created her husband Baron Limerick and Earl of Castlemaine in 1661. In many contemporary accounts, including Pepys's Diary, she is referred to as "Lady Castlemaine".