Descendant of a low-ranking samurai family, Sakamoto early established a reputation for swordsmanship. The contacts he made through his sword fighting served him in good stead when, influenced by imperial ideology, he began to plot against the Tokugawa shogunate for a restoration of power to the emperor.

By early 1862 Sakamoto had left his native han of Tosa and soon was helping the shogunal official Katsu Kaishū set up a naval training school. When Katsu was dismissed from his post, Sakamoto took refuge in Satsuma han, where antishogun sentiment had become widespread. Believing that restoration was possible only if the antishogun forces agreed to act in unison, Sakamoto persuaded the leaders of Satsuma to drop their historical enmity toward Chōshū. In his role as intermediary between the two hans, Sakamoto even arranged for Satsuma to aid Chōshū in obtaining British arms when the shogunate attempted to block foreign trade to that fief.

Sakamoto drew on his ancestors' merchant background to form a shipping company that doubled as a tiny navy. Rejoining his Tosa compatriots, he helped develop the program under which the lord (daimyo) of Tosa, Yamanouchi Yōdō, persuaded the shogun to resign and began planning for a new regime. Sakamoto was murdered by proshogunal samurai on the eve of the restoration.