Henry Shelton Sanford was born in Woodbury, Connecticut into an old New England family. His mother was Nancy Bateman Shelton. (Shelton Connecticut is named for one of her family members, Edward N. Shelton, founder of the Ousatonic Water Power Company)
Sanford’s father Nehemiah Curtis Sanford, a self-made millionaire who earned his fortune through the manufacturing of brass tacks. He was also a founder of Birmingham (Ansonia) Connecticut and a direct descendant of Thomas Wells, Governor of the Connecticut Colony. (The only person in Connecticut's history to hold all four top offices: governor, deputy governor, treasurer, and secretary.) and served in the Connecticut Senate for the 16th District.
Sanford began was the United States Secretary of the American legation to St. Petersburg, then Frankfurt and later, Paris. President Abraham Lincoln appointed him as Minister to Belgium in 1861.
Sanford coordinated northern secret service operations during the Civil War, arranged for the purchase of war materials for the Union in Europe, and delivered a message from Secretary of State William H. Steward to Giuseppe Garibaldi, offering the Italian patriot a Union command.
After the War, he bought an orange grove in St. Augustine, Florida, from John Hay, who had been one of President Lincoln's secretaries and later served as U.S. Secretary of State. It was the beginning of a Sanford’s large investment in the St. Augustine area.
In 1869, President Ulysses S. Grant nominated Sanford as his Minister to Spain but his Senate confirmation was tabled because, although Sanford wanted the post, he didn’t want to live in Spain.
The following year, 1870, Sanford paid $18,400 to former Confederate General Joseph Finegan to acquire his extensive land holdings along Lake Monroe and founded the city of Sanford, Florida.
He also had extensive holdings in the Congo and Belgian King Leopold II used Sanford to convince Henry Morton Stanley to explore the Congo basin for Belgium in 1878. He then hired Sanford in 1883 as his envoy to the United States to try to gain American recognition for his colony in Congo.
Sanford died at Healing Springs, Virginia on May 21, 1891. He is buried in Long Hill Cemetery, Shelton, Connecticut.