Among his siblings was elder brother, Sir Donald Macdonald, 4th Baronet, who participated in the Jacobite rising of 1689 and 1715.
[2] His paternal grandparents were Sir James Macdonald, 2nd Baronet (the eldest and only surviving son of Sir Archibald Macdonald, a Baron of the Exchequer) and Margaret Mackenzie.
His maternal grandparents were Robert Douglas, 8th Earl of Morton and the former Anne Villiers (a daughter of Sir Edward Villiers).
[2] Upon the death of his nephew, Donald in 1720, he succeeded as the 6th Baronet Macdonald, of Sleat, in the Isle of Skye, County Inverness, which had been created in the Baronetage of Nova Scotia in 1625.
Together, they were the parents of:[3] Sir James died in 1723 at Forres, Morayshire, and was succeeded in the baronetcy by his eldest surviving son, Alexander.