The daughter of Alfonso IV, duke of Modena, she grew up a devout Roman Catholic. The match with James was arranged through French diplomatic channels; they were married by proxy in September 1673, and she arrived in England in November. Although the English public regarded her as an agent of French and papal interests, her influence on her Roman Catholic husband's political thinking appears to have been negligible.

Between 1675 and 1682 Mary gave birth to five children, none of whom survived—with the blame popularly assigned to James's affliction with venereal disease in the 1660s. When her second son, James Francis Edward, was born on June 10, 1688, a month earlier than anticipated, it was widely, and falsely, rumoured that the child was not really hers but had been imposed upon the nation to ensure a Catholic succession to the throne. This suspicion gave the Protestant ruler William of Orange (William III), stadholder of Holland, a pretext to invade England in November 1688. Mary escaped to France with her son on December 11, and James followed shortly afterward.