His mother was a daughter of John Stewart, 1st Earl of Atholl, and Eleanor Sinclair.
William Murray inherited the main family residence at Tullibardine Castle, in the village of Tullibardine, 2 miles (3.2 km) north of Auchterarder, Perth and Kinross, from his grandfather (also William Murray) in 1525.
He was one of the Scottish aristocrats who accompanied Mary of Guise to France and England in 1550 at the conclusion of the war now known as the Rough Wooing.
In 1560, he was one of Lords of the Congregation who opposed Guise and French rule in Scotland.
He signed a commission for the Treaty of Berwick which facilitated to entry of an English army into Scotland to fight at the siege of Leith.