Humehume was born on Kauai in about 1797 to King Kaumuali‘i and, apparently, a commoner wife. Kaumuali‘i decided to send his son to America; he George was about six years old when he sailed into Providence, RI on June 30, 1805. He eventually enlisted in the US Navy and was wounded during the War of 1812. After the war, Humehume was taken under the wing of the ABCFM and was sent to be educated at the Foreign Mission School at Cornwall, CT.
He returned to the Islands with the Pioneer Company of American Protestant missionaries. Shortly following the death of his father, Humehume joined a group of Kauai chiefs in an unsuccessful rebellion. He was captured and spent the last 1½ years in custody; a victim of influenza, Humehume died on May 3, 1826, six years to the day of his return to Waimea, Kauai.