Harrison graduated from Yale College in 1895, where he was a member of the Psi Upsilon fraternity and the secret society Skull and Bones,[1]: 166  and from the New York Law School in 1897.

He later left to serve in United States Army during the Spanish–American War, as an assistant adjutant general with the rank of captain.

Harrison was governor-general of the Philippines from 1913 to 1921 and advocated for and oversaw the process of Filipinization, or the transfer of authority to Filipinos in the United States territory's Insular Government to better prepare for independence.

[3] His pro-Filipino stance made him a popular figure in the Philippines but also the object of criticism of conservative Americans who viewed his liberal governance as not supportive enough of U.S.

In 1936, Harrison expressed interest in acquiring Filipino citizenship but did not fulfill the required years of residency under the Naturalization Law.

From November 1946 to February 1947, Harrison served as commissioner of claims in the civil service of the United States Army in Manila.

After this latest service to the Philippines, Harrison retired to Spain for six years, then chose to move to Califon, New Jersey in August 1957.

[10] His only surviving son, Dr. Francis Burton "Kiko" Harrison, Jr., (1921–2014), was the subject of many photographs taken between 1939 and 1942 by the PaJaMa Collective and George Platt Lynes.

[12] His last wife, Maria Teresa Larrucea, a young Basque woman, was born in Amorebieta (Bizkaia, Spain) and outlived Harrison.