Born in Shewa Province, Imru was the childhood friend of his cousin; both were raised by Imru's father Haile Selassie Abayneh, whom Harold Marcus describes as the Emperor's "real father", noting "Makonnen's son recalled the surrogate with affection, whereas he invariably referred to his father with formality and deference. Both Imru and his father accompanied the future ruler to his first governorship in Sidamo. In 1916/17 Imru, by then a Dejazmach, was appointed governor of Harar by his cousin.
In 1932 he was promoted to Ras and made ruler of Gojjam province. Imru replaced Ras Hailu Tekle Haymanot, who had been convicted of treason for allegedly helping the deposed Lij Iyasu escape, and sentenced to life imprisonment. Upon arriving in Gojjam, Imru was immediately faced with a revolt by Fitawrari Admassu, a natural son of the imprisoned Ras, who on 30 September briefly held Debre Marqos; not long afterwards Admassu ended his revolt, sending messengers to the Emperor to ask for pardon. Nevertheless, despite numerous reforms and efforts to modernize the province, which enriched both the producers and traders, Imru found few friends in Gojjam and "was invariably viewed as an outsider, the emperor's agent, and, unable to rule by consensus, he governed by force.
In May 1935 Imru was appointed Regent. He led his provincial army and commanded the Army of the Left in the Second Italo-Abyssinian War. His early offensive deep into the Italian rear threatened the Italian advance but was stopped by the use of poison gas dropped from the air on December 23 1935.
After the defeat of the Ethiopian armies, Haile Selassie appointed his cousin as Prince Regent in his absence, departing Ethiopia with his family to present the case of Ethiopia to the League of Nations at Geneva. Ras Imru fell back to Gore in southern Ethiopia to reorganize and continue to resist the Italians. For this to have worked, he needed the revenue of the gold mines of Asosa, but the loyal Sheikh Hojali was driven out in July 1936 by rebellious Welega Oromo, who also made Ras Imru's position in Gore untenable, and he retreated to the southeast with the Italians following him, pinning him down on the north bank of the Gojeb River, where he surrendered December 19 1936. He was flown to Italy and imprisoned on the Island of Ponza until freed after the surrender of Italy.
After the war Ras Imru served as Ambassador to India and the United States. In his later life he and his son Mikael Imru became advocates for land-reform. After his death, he was given a state funeral by the Derg.