He was the son of Alexander Cunningham, 5th Earl of Glencairn and Janet Hamilton, daughter of James Hamilton, 1st Earl of Arran. He married sometime before 24 August 1549 to Janet Gordon of Lochinvar (died 18 November 1596). She was the daughter of Sir James Gordon of Lochinvar and Margaret Crichton. They had the following children:
- James Cunningham, 7th Earl of Glencairn
- John Cunningham, Laird of Ross
- Lady Jean Cunningham who married George Haldane of Gleneagles (died 18 October 1574). After his death she married Roger Kirkpatrick of Closeburn.
- Lady Katherine Cunningham who married Robert Fergusson, 9th Laird of Craigdarroch (died about 1613).
- Lady Margaret Cunningham who married Sir Lachlan Mor Maclean of Duart (died 5 August 1598)
- Lady Elizabeth Cunningham who married (1) in 1579 to James Crawford of Auchinames. After his death she married Alexander Cuninghame, 5th Laird of Craigends. Elizabeth died before 7 September 1614.
- Lady Susannah Cunningham who married John Napier of Kilmahew
William died between 1576 and 24 February 1579/80.
William is a 14th great-grandfather of Prince William, Duke of Cambridge.
|Offspring of William Cunningham, 6th Earl of Glencairn and Janet Gordon (-1596)|
|James Cunningham, 7th Earl of Glencairn (c1552-1630)|
|John Cunningham (c1554-)|
|Jean Cunningham (c1556-)|
|Katherine Cunningham (c1558-)|
|Margaret Cunningham (c1560-)|
|Elizabeth Cunningham (c1562-1614)|
|Susannah Cunningham (c1564-)||1564 Scotland||John Napier (-c1644)|