[4] She was born on May 12, 1843, the youngest daughter of High Chief Kūhiō Kalanianaʻole of Hilo, and Princess Kinoiki Kekaulike from Kauaʻi island.

Her mother was the stepdaughter of the Queen Regent Kaʻahumanu and the daughter of Kaumualiʻi, the last king of Kauaʻi before he agreed to be a vassal to Kamehameha I in 1810.

She handed the royal mantle to Chief Justice Albert Francis Judd who placed it on the king's shoulders "as of the Ensign of Knowledge and Wisdom".

[8][9] Princess Kekaulike started to suffer from what was termed a "heart disease", a year after Kalākaua's coronation, and during her illness received a visit from Mother Marianne Cope.

In her will, she gave her Beretania street residence Ululani, as the site of a proposed maternity home to help Hawaiian mothers, which later became the Kapiolani Medical Center for Women and Children.