Coote also sat as an MP, and held various senior administrative posts, including Lord President of Connaught.

He entered Trinity College, Dublin in 1622, was knighted in 1626, and was elected Member of Parliament for County Leitrim in the Irish House of Commons in 1640.

At this time Coote traveled to England with a number of Protestants to agitate for harsh anti-Catholic measures and an end to the cessation.

The execution of Charles I in 1649 led local Protestant and Scottish forces in Ulster to join the Duke of Ormond's royalist coalition, thus isolating Coote.

He defended Derry against a protracted siege (March–August 1649), with the unlikely assistance of the Irish Confederate Ulster army under Owen Roe O'Neill.

By early 1650, however, the Irish Ulster army (now under Heber MacMahon, as O'Neill had died a few months earlier) became active once more, and Coote was again forced onto the defensive.

After Cromwell's death, Coote took part in December 1659 in a coup d'etat against The Protectorate, seizing Dublin Castle.

However, deep divisions among the three men, particularly on the question of whether dispossessed Roman Catholics should be allowed to recover their lands, seriously weakened the effectiveness of the regime.