Born in Vincennes, Indiana, the son of future President William Henry Harrison and Anna Tuthill Symmes and the grandson of Declaration of Independence signer, Benjamin Harrison V, Harrison completed preparatory studies and studied medicine. He later abandoned this to become a farmer.
In 1824, he married Lucretia Knapp Johnson (16 September 1804 – 6 February 1830). They had three children:
After his father's death, in 1841, his mother moved in with his family to help raise the children.
He was elected a Whig to the U.S. House of Representatives in 1852, reelected an Oppositionist in 1854 and served from 1853 to 1857. After being defeated for a third term in 1856, Harrison retired to his estate "Point Farm" in North Bend, Ohio where he died on May 25, 1878. He was the last surviving child of William Henry Harrison. He was interred in the William Henry Harrison Tomb State Memorial in North Bend with his parents and other family members. Harrison's body was stolen by grave robbers until it was eventually returned to its final place of rest.