Mary was the only daughter and heiress of Sir John Clotworth of Antrim, 1st Viscount Massereene. On 20 July 1654 she married Sir John Skeffington, 2nd Viscount Massereene, who had succeeded his cousin as 4th Bt in April 1652, and his father-in-law on 23 September 1665 as 2nd Viscount. Mary died on 20 September 1686, and her husband died on 21 June 1695; he was succeeded by his only surviving son Clotworthy as 3rd Viscount Massereene.

Mary's father was Member of Parliament for Antrim for many years and was active during the Short and Long Parliaments in both political and religious affairs, frequently falling out with the government and the army. After the Restoration, which he was actively engaged promoting, he was elevated to the Irish peerage on 21 november 1666 as Baron of Loughneagh and Viscount Masereene.