In October 1917 he became Chief of Staff of the Irish Republican Army (IRA) and held that post until March 1919. In 1918 he was elected to Dáil Éireann representing Waterford and he soon became Minister for Defence. Due to the absence of Éamon de Valera and Arthur Griffith, Brugha presided over the first meeting of Dáil Éireann on the 21 January 1919.
He was known for his bitter enmity towards Michael Collins, who, although nominally only the IRA's Director of Intelligence, had far more influence in the organisation as a result of his position as a high ranking member of the Irish Republican Brotherhood, an organisation that Brugha saw as undermining the power of the Dáil and especially the Ministry for Defence. At a top-level IRA meeting in August 1920, Brugha argued against ambushes of Crown forces unless there was first a call to surrender, but this was dismissed as unrealistic by the brigade commanders present. Brugha also had the idea of moving the front line of the war to England, but was opposed by Collins.
On 7 January 1922 Brugha voted against the Anglo-Irish Treaty. During the Treaty Debates he pointed out that Collins only had a middling rank in the Department for Defence which supervised the IRA, and yet the newspapers were hailing him as 'the man who had won the war'. He left the Dáil and was replaced as Minister for Defence by Richard Mulcahy. On the outbreak of the Irish Civil War on 28 June 1922 he joined the anti-Treaty side, which had occupied buildings in O'Connell Street. In the first week of July Free State forces commenced shelling of the anti-treaty positions.
Most of the anti-treaty fighters under Oscar Traynor escaped from O'Connell Street when the buildings they were holding caught fire, leaving Brugha in command of a small rearguard. On 5 July he ordered his men to surrender. He then approached the Free State troops, brandishing a revolver. He sustained a bullet wound to the leg which 'severed a major artery causing him to bleed to death'. He died on 7 July 1922, just 11 days before his 48th birthday. He is buried in Glasnevin Cemetery.
His wife Caitlín Brugha served as a Sinn Féin TD from 1923–27. His son, Ruairí Brugha later became a Fianna Fáil politician and was elected to Dáil Éireann in the 1973 General Election.
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