He was born in London on 25 March 1806, and baptised at St James's Church, Piccadilly, the youngest son but one of Kenneth Francis Mackenzie (died 1831) and his wife, Anne Townsend.

Colin Mackenzie was educated successively at a school in Cumberland, at Dollar Academy, and at Oswestry, and in 1825 was appointed a cadet of infantry on the Madras establishment of the East India Company.

In this position he was deputed by Pottinger to convey letters to the political agent at Jellálabad and to General Sir George Pollock, who had reached that place.

Mackenzie was subsequently moved by Akbár Khán with the rest of the hostages and prisoners, over the Hindu Kúsh; but after the arrival of Pollock's force in the vicinity of Kábul, money was paid for their release.

Mackenzie had held his new command for some years when a mutiny occurred in one of the cavalry regiments of the contingent, in which he was wounded, in September 1855, on the occasion of the Muharram procession at Bolarum.

On that occasion, the governor of Madras, Francis, Lord Napier, and one of the members of council, referred the question to the secretary of state, who declined to interfere.

He married secondly, in 1843, Helen, eldest daughter of Admiral John Erskine Douglas, who survived him, and published several works relating to India, besides the life of her husband.