The story begins with a legal trick. In May 1861, three enslaved men named Frank Baker, Shepard Mallory, and James Townsend slipped across Hampton Roads to Fortress Monroe, the only Union-held fort on Virginia's southeastern coast. When their owner came to demand them back, fort commander General Benjamin F. Butler refused. The fugitive-slave law required him to return them, Butler reasoned, but the Confederacy had declared itself a foreign nation, and slaves were being used to build Confederate fortifications - so they were "contraband of war." The phrase stuck. Within months, thousands of people seeking freedom arrived at the fort. The Army built them a settlement from the burned timbers of Hampton itself, which Confederate troops had torched on retreat. They called it the Grand Contraband Camp, and locally, Slabtown. It was the first self-organized African American community in the United States.

After the war, the American Missionary Association formalized the work Mary Peake had begun. In April 1868, on the grounds of a former plantation called Little Scotland overlooking the Hampton River, the Hampton Normal and Agricultural Institute opened its doors. Its first principal was Samuel Chapman Armstrong, a 28-year-old former Union brigadier general who had commanded U.S. Colored Troops at Petersburg. Armstrong's pedagogy was rigid and paternalistic by modern standards - he believed in industrial training over liberal arts, and his curriculum drew sharp criticism from W.E.B. Du Bois decades later. But Hampton survived where many freedmen's schools failed, and it produced graduates who shaped American education for a century. Among the first students was a young man from West Virginia who had walked most of the way to enroll: Booker T. Washington. He graduated in 1875 and went on to found Tuskegee Institute, where he would build a sister institution modeled on what he learned at Hampton.

In 1878, Hampton expanded its program to include Native American students - initially seventy-two warriors held as prisoners of war from the Cheyenne, Kiowa, Comanche, and Caddo nations, who had been incarcerated at Fort Marion in St. Augustine. Lieutenant Richard Henry Pratt convinced seventeen of the younger men to enroll at Hampton. By 1880 the school had about seventy Native students, mostly from the Plains. The program was conceived in the era's coercive framework of "civilization" through education, and its records make for hard reading today. It ended in 1923, after Jim Crow consolidated and white employers began refusing to hire Native men who had studied alongside Black classmates. The school's records, including ledger art produced by students and prisoners and now held at the Smithsonian, are a reminder that the institution's history is not a single triumphant narrative but a tangle of survival, ambition, and the violence of its time.

By 1872 Hampton was nearly broke. Armstrong hired Thomas P. Fenner to form the Hampton Singers - originally called the Hampton Jubilee Singers - modeled on the wildly successful Fisk Jubilee Singers tour of 1871. The Hampton choir toured the North performing spirituals to mixed audiences, and the donations they collected paid for the construction of Virginia Hall, the first dormitory for women on campus. The choir kept the school alive through the 1870s. The students themselves built much of the campus brick by brick. By 1900 Hampton was the wealthiest school serving African Americans in the country.

The 314-acre campus along the Hampton River was designated a National Historic Landmark District in 1974. The Emancipation Oak still stands and was cited by the National Geographic Society as one of the ten great trees in the world; the City of Hampton uses it on its official seal. The Hampton University Museum, founded in 1868, is the oldest African American museum in the United States and holds more than 9,000 pieces. The campus is also home to the Hampton University Proton Therapy Institute, the largest free-standing proton-beam cancer treatment facility in the world. Hampton became the first and only HBCU to lead 100 percent of a NASA mission. In 2020, philanthropist MacKenzie Scott donated $30 million - the largest single gift in the university's history. William R. Harvey retired as the school's 12th president in June 2022 after 43 years; he was succeeded by Darrell K. Williams, a 1983 graduate.