Upshur's namesake was born John Henry Nottingham in Northampton County, Virginia on 05 December 1823, probably at the plantation house "Selma," near Eastville. His parents were John Evans Nottingham and Elizabeth Parker Upshur, both from long established families that had settled Virginia's Eastern Shore in the early 17th century. He attended the College of William & Mary in 1837-40 before being accepted to the newly founded Naval Academy. Prior to entering the service, and his father having died when he was a young boy, his mother had John Henry's surname changed by act of Virginia Legislature to her maiden name of Upshur in order to benefit from her family's notable Naval tradition (her two brothers were Commander George Parker Upshur, USN, soon to be commandant of the Naval Academy, and Abel Parker Upshur, US Secretary of State).

Appointed a Midshipman 04 November 1841, the newly named Upshur reported to the Receiving ship at Norfolk before being ordered to the sail frigate Congress in April. He served aboard her for more than two years, on a Mediterranean cruise and off South America. Returning to America aboard United States in October 1844, Upshur was soon ordered to the new sloop-of-war St. Mary's. Initially intended for the Mediterranean Squadron, the sloop was instead sent to the Gulf of Mexico to support American interests in the rising tensions with Mexico over Texas. St. Mary's cruised in the Gulf of Mexico until the outbreak of the Mexican War, whereupon she began blockading the port of Tampico in May 1846, aiding in the occupation of that port in November 1846. Upshur served ashore with the naval battery during the siege of Veracruz in March 1847. Returning to Norfolk in May, he was detached and sent to the "naval school" at Annapolis, where he served until August 1848, after which he was assigned to the Naval Observatory in Washington. In June 1849, he was detached to report to frigate Cumberland, where he was warranted a Passed Midshipman 29 September 1849 (to date from 10 August 1847).

Sailing with Cumberland in the Mediterranean for two years, Upshur returned to New York City aboard Constitution in January 1851. He served on ordnance duty at Norfolk until being attached to store ship Supply in March 1852. Assigned to the West India Squadron, Supply supported Perry's expedition to Japan, returning to New York in February 1855. Upshur spent the next two years on ordnance duty at Washington Navy Yard, being promoted to Master 18 July and then Lieutenant 14 September 1855. Assigned once again to frigate Cumberland in June 1857, Upshur served as Flag Lieutenant of the Africa Squadron for the next two years.

Detached from Cumberland in September 1859, Upshur next served as an instructor at the Naval Academy, in which capacity he was serving when the Civil War began. Though a Southerner by birth, Lieutenant Upshur remained loyal to the Union. "My devotion to the country during the rebellion was the means of parting me from my birthplace, destroying old and valued friendships, and severing some of the tenderest and dearest ties of my life. None but those who experienced it can appreciate the sacrifice offered upon the altar of the country." Ordered as executive officer of steam frigate Wabash, just completing a refit at New York Navy Yard, Upshur served aboard her at the capture of Hatteras Inlet in August 1861 and that of Port Royal in November. Detached from her at the start of 1862, he was next ordered to command of screw steamer Flambeau, serving aboard her in the blockade of Charleston, taking several prizes, until September 1863. During his command, he was promoted to Lt. Commander 18 April 1863 (to date from 18 July 1862).

After a brief stint on ordnance duty at Philadelphia, Upshur next served in a choice assignment as commanding officer of screw frigate Minnesota, the flagship of the North Atlantic Blockading Squadron, from November 1863. While in command, Minnesota survived an attack by the Confederate torpedo boat Squib off Newport News, 09 April 1864. In September, Upshur was given command of the sidewheel steamer and former blockade runner A.D. Vance, serving at both the unsuccessful attack on Fort Fisher in December 1864, and that fort's successful capture a month later. Admiral Porter recommended him for promotion for his service during the latter attack: "in the Advance, [Upshur] had charge of the reserves and was employed day and night in landing army stores and guns, and covering the troops. His guns did good execution, and though his duties prevented from participating in the attack on the forts, I cannot withhold his name, and recommend him for advancement."

Decommissioned for a refit at New York in March 1865, Upshur's command was recommissioned with the new name Frolic in June. He served in her on European Station until September 1867, being promoted to Commander 07 August 1866 (to date from 25 July). Returning stateside, Commander Upshur commanded the apprentice ship Saratoga from September 1867 to April 1869. he was then ordered to "special duty" at naval station New London. While serving there in June 1869, Upshur was court-martialed on the charge of attempting to buy his son a place at the Naval Academy. Found guilty in part, he was sentenced to be censured by the Secretary of the Navy. This black mark appears to have had little impact on Upshur's career, and it appears his contemporaries understood he was a loving father desirous of having his son follow in his career path, who was taken advantage of by a con-man exploiting the corruption of the Grant administration. (As it happened, his son, Custis Parke Upshur, did enter the Academy with the Class of 1873, but failed to graduate).

Promoted to Captain 31 January 1872, Upshur commanded Pensacola, flagship of the Pacific Squadron from October 1872 to August 1873. After a period as executive officer of naval station New London, he next served in the South Atlantic as commanding officer of Brooklyn, flagship of the Atlantic Squadron, from May 1875 to July 1876. A series of shore assignments followed these prestigious commands: the Naval Academy board of examination, and member, Board of Naval Inspectors (March 1877-March 1880), followed by a lengthy leave of absence in Europe during 1880-1881. During this leave, he was promoted to Commodore in July 1880. Upshur then served on the Naval Examining Board before being appointed commandant of Brooklyn Navy Yard, 01 April 1882. His final command was commanding the Pacific Squadron, with his flag on Hartford, from spring 1884 to May 1885. Promoted to Rear Admiral 01 October 1884, Admiral Upshur was placed on the retired list, 01 June 1885. After 44 years of naval service, he spent a quiet retirement, dying in Washington, DC, 30 May 1917, just as America entered another conflict. He is buried in Arlington Cemetery.

At the annual dinner of the Graduates' Association of the U.S. Naval Academy in 1903, Admiral Upshur spoke these words, which our current naval officers would do well to consider:

"We of the Navy and Army are the only persons in our broad land who can be tried before a court of competent jurisdiction and punished for conduct unbecoming an officer and a gentleman. That we can carry on our daily work undismayed by this weighty burden of obligation is mainly due to the fruitful example of such men as our presiding officer, who are at once able seamen, brave and skilful officers, dignified, polished and accomplished men of the world. His is a type which the service must ever hold in high esteem, just as he himself is so held by those who like myself have enjoyed, and we trust, profited by the great privilege of serving under his command."