Born on March 26, 1861 (Bunkyu 1) in Koishikawa, Edo, as the eldest son of Uchimura Yoshiyuki, a samurai of Takasaki Domain. Through the Tokyo School of English (today Aoyama Gakuin), in 1877 (Meiji 10) he entered the Sapporo Agricultural College (today Hokkaido University) in its second class. Classmate of Nitobe Inazo and Miyabe Kingo, he graduated first in his class with a degree in agriculture. During his studies, in 1878, he was baptized by the Methodist Episcopal missionary M.C. Harris and became a Christian. The 'Covenant of Believers in Jesus' signed with his classmates is the origin of collective Christian vows in Japan. In 1884 he traveled to the U.S. and at Amherst College experienced a deep conversion through President J.H. Seelye, gaining his Bachelor of Divinity in 1887 and studying at Hartford Theological Seminary. After returning home in 1888, he became a contract teacher at the First Higher Middle School. On January 9, 1891, at the school's ceremony to read the Imperial Rescript on Education, he declined the deepest bow to the rescript (he bowed deeply but not in the manner of the deepest reverence), which became the great 'Lèse-majesté Incident' and drove him from his post. Thereafter he was a freelance Christian and writer, publishing one important work after another: 'Consolations of a Christian' (1893), 'Record of Seeking Peace' (1894), 'How I Became a Christian' (1895 in English), founding the journal 'Biblical Research' (1900), and 'Representative Men of Japan' (1908 in English). He advocated 'Mukyokai' (Non-Church Christianity), developing his own form of faith relying not on institutional churches, clergy, baptism, or communion but only on the Bible and faith. During the Russo-Japanese War (1904–05) he championed anti-war views, joining forces with socialists like Kotoku Shusui. In his late years he led a 'Second Coming movement,' awaiting Christ's return. He died of heart failure in Kashiwagi, Tokyo on March 28, 1930, aged 69.

A stern, passionate, prophetic Christian. With the mettle not to bow to authority, in the full tide of Meiji nationalism he held to anti-establishment positions — declining the imperial bow, opposing the Russo-Japanese War. He took pride in a 'Christianity grafted onto the spirit of Bushido' and sought a Japanese way of being Christian. Gifted in writing, he left excellent works in both English and Japanese. His disciples called him a 'Christian samurai.'

Uchimura's 'Mukyokai' is a uniquely Japanese Christian movement carried on across generations, producing disciples such as Yanaihara Tadao, Nanbara Shigeru, Tsukamoto Toraji, Masaike Jin, Sekine Masao, Asami Sensaku, and Fujii Takeshi. 'Representative Men of Japan,' his English-language work, introduced Saigo Takamori, Uesugi Yozan, Ninomiya Sontoku, Nakae Toju, and Nichiren to the Western world, and alongside Nitobe Inazo's 'Bushido' and Okakura Tenshin's 'Book of Tea' it is internationally esteemed as one of the 'three works introducing Japan in English.' His creed of devoting his life to the 'two J's' (Jesus and Japan) is the origin point of Japanese Christianity. The Lèse-majesté Incident is deeply engraved in the history of modern thought as a symbol of the clash between Christianity and state Shinto.