MacDonagh was a member of the Gaelic League. He was assistant head teacher at Patrick Pearse's St. Enda's school, lectured in English at U.C.D., and was a published poet. He was also a founding member and editor of the literary monthly 'Irish Review', and established the Irish Theatre on Hardwicke Street.
MacDonagh was active in the Irish Women’s Franchise League set up in 1911, and he was a member of the Dublin Industrial Peace Committee during the 1913 labour dispute. He joined the Irish Volunteers on their formation in November 1913. In March 1915 he became commandant of the 2nd Battalion of the Dublin Brigade.
As one of the four Dublin battalion commandants, he took an active part in the Rising, being in charge at Jacob's biscuit factory in Bishop Street. Mainly because of its location in a densely built-up area providing no easy approach, Jacob's was not directly assaulted. When Pearse’s surrender order reached the garrison on Sunday, 30 April 1916, MacDonagh and his men were initially reluctant to comply.