Born at Fort Apache, Arizona Territory Upham was appointed to the United States Naval Academy on 6 September 1889 and graduated on 2 June 1893.

At the time of the Spanish–American War, Upham was on the staff of the Commander in Chief, Asiatic Squadron, Commodore George Dewey; and the young officer received his baptism of fire during the Battle of Manila Bay.

During the years before World War I, Upham's sea duty embraced tours in the battleships Oregon, New Jersey, and South Dakota; he also commanded Olympia and the yacht Scorpion.

During World War I, Upham commanded the cruisers Columbia and Pueblo and earned the Navy Cross for leading the latter during the "difficult, exacting, and hazardous" convoy escort missions across the Atlantic.

Given the temporary rank of admiral on 18 August 1933, Upham returned to the Far East as lllCommander in lllChief, Asiatic Fleet, and broke his flag in the heavy cruiser Augusta commanded by then-captain Chester W. Nimitz.