The Harbor Defenses of Portsmouth was a United States Army Coast Artillery Corps harbor defense command. It coordinated the coast defenses of Portsmouth, New Hampshire and the nearby Portsmouth Naval Shipyard in Kittery, Maine from 1900 to 1950, both on the Piscataqua River, beginning with the Endicott program. These included both coast artillery forts and underwater minefields. The command originated circa 1900 as the Portsmouth Artillery District, was renamed Coast Defenses of Portsmouth in 1913, and again renamed Harbor Defenses of Portsmouth in 1925.

The first fort in the Portsmouth area was Fort William and Mary (called The Castle until circa 1692) in New Castle, initially garrisoned before 1632 and perhaps the oldest continuously fortified site in the British colonies that later became the United States. In 1680 another small fort was established on the site of the later Fort McClary in Kittery, Maine, then a part of Massachusetts. This was called Fort Pepperrell after its builder, William Pepperrell. In 1720 this became a permanent battery of six guns named Fort William.

In 1746 Battery Cumberland was built at Jaffrey's (Jerry's) Point in New Castle. Both Fort William and Mary and Fort William figured in the American Revolution. On 14–15 December 1774 Fort William and Mary was raided twice. On the first night a large group of patriots led by John Langdon overpowered a six-man caretaker detachment and confiscated much of the fort's supply of gunpowder. On the second night another raid under John Sullivan seized 16 of the fort's cannon and a number of muskets. These raids were the first acts of the Revolution in New Hampshire. In 1775 Fort William was seized by New Hampshire militia and expanded. The British recaptured Fort William and Mary, but eventually abandoned it and New Hampshire; the Patriot forces probably renamed it Fort Hancock.

Other forts built during the Revolution in the Portsmouth area included Fort Washington on Peirce Island in Portsmouth and Fort Sullivan on Seavey's Island in Kittery, near the later site of the Portsmouth Naval Prison. Both were built in 1775 and were named for George Washington and local hero John Sullivan. Fort Washington was a star-shaped earthwork. Both forts were commanded by Captain Titus Salter (or Salten) during the Revolution. They were re-garrisoned in the War of 1812 and abandoned after that war.

Following the Revolution Fort William and Mary was called Castle Fort or Fort Castle. In 1794 the United States Army took over the fort as part of the first system of US fortifications, adding a two-story blockhouse. In 1808 the fort was rebuilt and renamed Fort Constitution while Fort McClary was constructed across the river, both of these under the second system of fortifications. Around this time Battery Cumberland was rebuilt with stone as the Fort at Jaffrey's Point. A Martello tower was added to Fort Constitution during the War of 1812, while a blockhouse was added to Fort McClary in 1844. Major expansions of both forts were begun during the Civil War under the third system of forts, but were abandoned incomplete in 1867; war experience showed that masonry forts were too vulnerable to rifled cannon. Fort Constitution's north front was demolished to prepare for the third system expansion. Fort Sullivan at the Navy Yard was rebuilt in 1861 with eleven 8-inch Rodman guns. In the 1870s Jaffrey's (Jerry's) Point became the center in the Portsmouth area of a soon-abandoned rebuilding of the US fort system, with a 12-gun earth-protected battery called the Battery at Jerry's Point.

As recommended by the Endicott Board of 1885, construction began in 1898 on three forts to defend the Portsmouth area. Fort Stark on Jaffrey's Point was the largest, Fort Foster in Kittery was second, and two new batteries were built adjacent to Fort Constitution. An underwater minefield also guarded the harbor, initially controlled from a mine casemate at Fort Stark. Before much work had been done the Spanish–American War broke out in 1898. Emergency batteries were constructed to quickly arm key points, as most of the Endicott batteries were still years from completion and it was feared the Spanish fleet would bombard the US East Coast. The batteries built for Portsmouth were at Fort Stark, with two 8-inch (203 mm) M1888 guns mounted on converted carriages built for Rodman guns in the 1870s emplacements, and at Fort McClary, with three 15-inch (381 mm) Rodman guns. A Civil War-era battery of four 100-pounder (6.4-inch, 163 mm) Parrott rifles at Fort Constitution was also available. The 8-inch guns were removed in 1900 to arm new Endicott batteries elsewhere and to make room for the new batteries at Fort Stark; the 15-inch guns and Parrott rifles remained at least through the end of 1903. The forts were completed in 1905. Fort Stark had two 12-inch (305 mm) guns and two 6-inch (152 mm) guns, all on disappearing carriages, with four 3-inch (76 mm) guns to defend the minefield against minesweepers. Fort Foster had three 10-inch (254 mm) disappearing guns and two 3-inch guns. Fort Constitution had two 8-inch disappearing guns and two 3-inch guns.

The American entry into World War I brought many changes to the Coast Artillery and CD Portsmouth. As the only component of the Army with heavy artillery experience and significant manpower, the Coast Artillery was chosen to operate almost all US-manned heavy and railway artillery in that war. Stateside garrisons were drawn down to provide experienced gun crews on the Western Front. Some weapons were removed from forts with the intent of getting US-made artillery into the fight. 8-inch, 10-inch, and 12-inch guns and 12-inch mortars were converted to railway artillery, while 5-inch and 6-inch guns became field guns on wheeled carriages. However, few railway artillery pieces were mounted and few or none saw action before the Armistice. The remounted 5-inch and 6-inch guns were sent to France, but their units did not complete training in time to see action. All three 10-inch guns from Fort Foster, both 8-inch guns from Fort Constitution, and both 6-inch guns from Fort Stark were removed; after the war the 10-inch guns were returned, but the 6-inch guns were stored and the 8-inch guns probably became railway artillery. At all the forts, numerous temporary buildings were constructed to accommodate the large influx of new recruits. Camp Langdon (named for the Revolutionary War hero and originally the New Military Reservation) was established in New Castle due to insufficient space at the forts. References indicate the authorized strength of CD Portsmouth was 10 companies, including four from the New Hampshire National Guard.

In 1920 a new mine casemate was built at Fort Constitution to replace the one at Fort Stark. On 1 July 1924 the harbor defense garrisons completed the transition from a company-based organization to a regimental one, and on 9 June 1925 the commands were renamed from "Coast Defenses..." to "Harbor Defenses...". The Harbor Defenses of Portsmouth (HD Portsmouth) appears to have been in caretaker status for most of the interwar period. Though most of the regiment was in the Harbor Defenses of Portland (Maine), the 8th Coast Artillery was also the Regular Army component of HD Portsmouth from 1 July 1924 through early 1940, when the new 22nd Coast Artillery assumed that duty; there does not appear to have been a National Guard harbor defense regiment in the area. Camp Langdon received a battery of two fixed antiaircraft guns in 1920; these were probably the 3-inch gun M1917 and were removed in the early 1930s.