Enomoto was born as a member of a samurai family in the direct service of the Tokugawa clan in the Shitaya district of Edo (modern Taitō, Tokyo).

During his stay in Europe, Enomoto had realized that the telegraph would be an important means of communication in the future, and started planning a system to connect Edo and Yokohama.

During the Meiji Restoration, after the surrender of Edo in 1868 during the Boshin War to forces loyal to the Satchō Alliance, Enomoto refused to deliver up his warships, and escaped to Hakodate in Hokkaido with the remainder of the Tokugawa Navy and a handful of French military advisers and their leader Jules Brunet.

Enomoto hoped to create an independent country under the rule of the Tokugawa family in Hokkaidō, but the Meiji government refused to accept partition of Japan.

However, the leaders of the new Meiji government (largely at the insistence of Kuroda Kiyotaka) realized that Enomoto's various talents and accumulated knowledge could be of use, and pardoned him in 1872.

Two years later, after leaving the government, Enomoto also helped to establish a private organization, the "Colonial Association", to promote external trade and emigration.