Born in Lowell, Massachusetts, Pillsbury was appointed midshipman in 1862 and commissioned an ensign in 1868.

After serving on various stations afloat and ashore, he commanded the coast steamer Blake from 1884 to 1891 and did excellent scientific work, using some of his research instruments of his own invention.

In the Spanish–American War, he commanded the dynamite cruiser Vesuvius, operating around the island of Cuba and in the vicinity of Morro Castle.

Although Rear Admiral Pillsbury's attainments as a sailor and a fighting man were noteworthy, he is perhaps best known as having been one of the world's foremost geographers and an authority on the Gulf Stream.

Pillsbury Sound, the body of water in the U.S. Virgin Islands between St Thomas, St John, and the cays which bound the sound on the North side,[3] is also named in his honor.