Son of Kenneth Mackenzie (d. 1761) and Mary Stewart. Married (1765) to Caroline Stanhope (1746-1767). In 1766 he was granted the titles of Viscount Fortrose and Baron Ardelve, and in 1771 he was granted the title of Earl of Seaforth, a title which had previously been held by his family but had been attainted due to his grandfather's role in the Jacobite uprising of 1715. Thus he was the 5th Earl of Seaforth in total, but the 1st Earl of the 2nd Creation.
He served as the Member of Parliament for Caithness from 1768 until 1774.
In 1771 Mackenzie raised a regiment known as the 78th Regiment of Highlanders, of which he himself became Colonel. The regiment stayed for some time at the Channel Islands before, in June 1781, they embarked for India. This journey was to prove fatal for Mackenzie, who died even before they reached their destination.
He had been forced to sell his estates to cover debts in 1779. Following his death, what was left was inherited by his only child, Caroline Mackenzie (1766-1847), and his titles became extinct.
Boswell had breakfast in the company of Mackenzie at Brunswick on June 27, 1764. He described him as “a lively, pretty young man, with the most perfect elegance of manners, having been abroad a great many years.”