He was born in Siberia in 1797 to a clerical family, and became a married parish priest in Irkutsk. A devout explorer, John Kriukov, told him of the great spiritual needs among the Russian and native peoples in Alaska, then Russian territory. Moved to serve Christ in this very difficult environment, he and his family arrived in Alaska in 1824. He quickly learned the Aleut language and worked humbly and tirelessly among the Aleuts. His spiritual classic, An Indication of the Way to the Kingdom of Heaven, was originally written in Aleut and later translated into many languages.

While he was visiting Russia in 1838, his wife died; one year later he was tonsured a monk and given the name of Innocent (he had been Fr John Veniaminov). Almost immediately after his tonsuring he was, without warning, raised to the rank of Bishop of all Eastern Siberia and Russian America, probably the largest diocese in the world at that time. Returning to Alaska, he continued his missionary work with vigor, often traveling among Aleut and Tlingit settlements in his own kayak. Wherever he went, he found the Alaskan people hungry for the faith, and his labors bore rich fruit which is still obvious today: Alaska has more Orthodox churches per capita than any other state.

In old age he was made Metropolitan of Moscow, head of the entire Russian Orthodox Church. His concern for Christian mission was undiminished, and as Metropolitan he created the Orthodox Missionary Society. He reposed on Holy Saturday of 1879.