[2] He was born in the small Honolulu neighborhood of Kakaʻako to Emily (Honey) Leimaile Silva and James Ah You Puao Ho, but he grew up in Kāneʻohe on the windward side of the island of Oʻahu.

He was a graduate of the Kamehameha Schools in 1949 and he attended Springfield College on a football scholarship in 1950, but he returned home to earn a Bachelor's degree in sociology at University of Hawaiʻi in 1953.

Transferred to Travis Air Force Base, California, he went to the local city of Concord and bought an electronic keyboard from a music store, and recalls, "That's when it all started."

Ho left the Air Force in 1959 due to his mother's developing illness and began singing at her club in Kaneohe.

[3] He released his debut album, The Don Ho Show!, in 1965 and began to play high-profile locations in Las Vegas, Lake Tahoe and New York City.

From 1964 to 1969, Don's backing group was The Aliis: Al Akana, Rudy Aquino, Benny Chong, Manny Lagodlagod and Joe Mundo.

During the second half of the decade, a growing movement emerged in Hawaii to produce more traditional forms of music that subtly accused Ho of being too commercialized and marketed to tourists.

Guest appearances on television series such as I Dream of Jeannie, The Brady Bunch, Sanford and Son, Batman, Charlie's Angels, McCloud and Fantasy Island soon followed.

Although his album sales peaked in the late 1960s, he was able to land a television series on ABC from October 1976 to March 1977 with The Don Ho Show variety program which aired on weekday mornings.

He also continued his nightly performances making a few concessions, such as trading in his glass of Scotch, which he kept on top of his piano at shows, for pineapple juice.

On December 6, 2005, Ho had his own blood-derived stem cells injected into his heart by Amit Patel and his fellow surgeons in Thailand.

[26] Since Ho's death, his estate has been in limbo because of numerous management conflicts[27] and legal changes that transpired while he was struggling with his mental and physical health.