Esther Kia'āina was born in Guam to parents Lorelei Haunani Kia'āina and Melvin Leialoha Kia'āina. Before she was born, her parents left Hawaii due to her father being stationed in Guam while serving in the U.S. Navy. Kia'āina moved to Oahu in 1978, graduating from Kamehameha Schools in 1981.
Kia'āina received her B.A. from the University of Southern California in international relations and political science. She then attended George Washington University to receive her J.D. and Johns Hopkins SAIS to receive her M.A.
After graduating from the University of Southern California in 1985, Kia'āina served as an intern to then-Senator Daniel Inouye in Washington, D.C. She also worked for then-Senator Daniel Akaka during the 1990s, and as a Chief of Staff for Congressman Robert Underwood of Guam and former Congressman Ed Case.
In Hawaii, Kia'āina served as a Land Asset Manager at her alma mater Kamehameha Schools for two years before moving on in 2009 to work for the Office of Hawaiian Affairs.
In 2012, Kia'āina ran to represent Hawaii's 2nd congressional district in the United States Congress, following the retirement of Congresswoman Mazie Hirono, who had decided to run for United States Senate following the retirement of Senator Akaka. She was one of six candidates and placed third with 10% of the vote, losing to Congresswoman-elect Tulsi Gabbard, and former Mayor of Honolulu Mufi Hannemann.
On October 15, 2012, Neil Abercrombie, the Governor of Hawaii, appointed her to the Hawai'i Department of Land and Natural Resources, an office that was left vacant following the resignation of Guy Kaulukukui.
Following the death of Senator Inouye, who had represented the state of Hawaii since its founding, the Hawaii Democratic Party was given the ability to choose three possible replacements to recommend to Governor Abercrombie. On December 26, 2012, the party met and chose the three contenders. Kia'āina, Congresswoman Colleen Hanabusa (Inouye's requested choice), and Lieutenant Governor of Hawaii Brian Schatz were selected for recommendation. To prevent a long vacancy during the United States fiscal cliff budget negotiations, Abercrombie made his decision quickly, per request of U.S. Senate Majority Leader Harry Reid: Schatz was chosen to fill Inouye's seat until a special election in 2014.
Kia'āina was nominated by President Barack Obama to lead the Office of Insular Affairs as Assistant Secretary of the Interior for Insular Areas on September 11, 2013. She was confirmed by the U.S. senate on June 26, 2014. In May 2016, Obama designated Kia'āina as the White House representative for the Northern Mariana Islands.