He was initially named Kalahoʻolewa meaning "the day of the funeral" in Hawaiian because his birth coincided with the funeral of King Kamehameha III. He was the youngest brother of James Kaliokalani, David Kalākaua, Liliʻuokalani, Anna Kaiulani, Kaʻiminaʻauao, and Miriam K. Likelike. Shortly after his birth he became the hānai (adopted son) of Princess Ruth Keʻelikōlani who named him after her late husband High Chief William Pitt Leleiohoku. Leleiohoku means "Fled in the time of Hoku" in Hawaiian and commemorates the day Kamehameha I died on the Hawaiian calendar.:212 Princess Ruth also named Leleiohoku II heir to her vast holding of most of the Kamehameha lands but he predeceased her. He was educated at the present day ʻIolani School, which was called the Saint Alban's College at the time. An accomplished musician, he founded several royal choral societies that survive today including the Kawaihaʻo Church Singing Club. He was named the Crown Prince by his brother Kalākaua in 1874, with the consent of the House of Nobles and granted the title of Prince and style of "His Royal Highness". He became a member of the Privy Council and House of Nobles and ruled as Prince-regent when Kalākaua visited the United States.
On April 10, 1877 at the age of 23, Prince Leleiohoku died of rheumatic fever. Because Leleiohoku was unmarried and had no children, his brother King Kalākaua named their sister Liliʻuokalani Crown Princess. It was said that Keʻelikōlani had wished that Kalākaua had chosen her instead of Liliʻuokalani, but making her heir would make Bernice Pauahi Bishop next in line to the throne. He is buried in the Royal Mausoleum of Hawaii.