Born in 1836 into a gokenin family of the Edo Shogunate, he studied navigation at the Nagasaki Naval Training Institute and went to study in the Netherlands, mastering modern naval technology. In the Boshin War (1868) he led the shogunal navy's defecting fleet as vice-president of the shogunal navy, crossed to Ezo (Hokkaido), and made Goryōkaku his base. In 1869 he was elected president of the Republic of Ezo (comprising Matsumae domain and former shogunate forces), but surrendered to the new government forces (Battle of Hakodate). After surrendering he was imprisoned, but was released when the Meiji government recognised his talents as a naval engineer. He subsequently held important posts including Navy Minister, Minister of Communications, and Minister of Agriculture and Commerce, and contributed to concluding the Treaty of Saint Petersburg (1875) exchanging Sakhalin and the Kuril Islands with Russia. He is known as a symbol of conversion who contributed to Meiji technology and diplomacy. He died in 1908, aged 72.

A man in whom the positivist thinking of an engineer and a sense of duty and loyalty to the former shogunate were intricately intertwined. The establishment of the Republic of Ezo was not simply an anti-new-government movement; it also had the practical aims of improving the treatment of former shogunate warriors and developing the undeveloped lands of Ezo. After his surrender he flexibly cooperated with the new government and contributed to the modernisation of Meiji Japan — showing a pragmatic side as well. His life was a constant search for arenas in which to make maximum use of his technical skills and knowledge.

The Battle of Hakodate is remembered in history as Japan's last civil war, and Goryōkaku in Hakodate, Hokkaido remains popular as a tourist destination today. Though the Republic of Ezo was short-lived, it is assessed as a modern organisation that chose its leader by democratic election. His achievements in the Meiji government after his surrender demonstrated outstanding talent as an engineer and diplomat. Enomoto is known as a representative figure of former shogunate retainers who transitioned into the Meiji government.