He inherited his title on the death of his brother William O'Brien, 2nd Marquess of Thomond As a captain's servant, he entered the navy on 17 April 1783 on board HMS Hebe, stationed in the Channel.

From 1800 to 1804 he commanded Emerald on the West Indies station, where, on 24 June 1803, he made a prize of L'Enfant Prodigue, a French national schooner of sixteen guns, and in the spring of 1804 distinguished himself in forwarding the supplies at the capture of Surinam, as well as by defeating a projected expedition by the enemy against Antigua.

On 29 November 1809 he was granted a Royal Warrant of Precedence as if his father had succeeded to the marquisate of Thomond, and was henceforth known as Lord James O'Brien.

He succeeded his brother, William O'Brien, on 21 August 1846 as the third Marquess of Thomond.

[3] He married, first, on 25 November 1800, Eliza Bridgman, second daughter of James Willyams of Carnanton, Cornwall (she died on 14 February 1802); secondly, in 1806, while in the West Indies, Jane, daughter of Thomas Ottley, and widow of Valentine Horne Horsford of Antigua (she died on 8 September 1843); and, thirdly, on 5 January 1847, at Bath, Anne, sister of Sir C. W. Flint, and widow of Rear-Admiral Francis William Fane.