Mackenzie was the eldest son of Major William Mackenzie (died 12 March 1770), by Mary, daughter and heiress of Matthew Humberston of Humberston, in Lincolnshire.

Mackenzie adopted the additional name of Humberston on succeeding to his mother's property and purchased the remaining ancestral estates of the Earls of Seaforth from his cousin.

The regiment, initially staffed by Clan Mackenzie officers, became the 78th Foot later that year.

Mackenzie became a major in that regiment in 1779 and was present with five companies at the repulse of an attempted French landing in St Ouen's Bay, Jersey, on 1 May 1779.

On Lord Seaforth's death Humberston was transferred to the 78th regiment as lieutenant-colonel commandant in his place, 15 Feb.