During the 1810s the skins of Antarctic Ocean seals were highly valued as items for trade with China. As a skilled and fearless seal hunter, Palmer achieved his first command at the early age of 21. His vessel, a diminutive sloop named the Hero, was only 47 feet (14 m) in length. Palmer steered southward in the Hero at the beginning of the Antarctic summer of 1820–1821. Aggressively searching for new seal rookeries south of Cape Horn, on November 17, 1820, young "Captain Nat" and his men became the first Americans to discover the Antarctic Peninsula. After much larger ships skippered by Fabian Gottlieb von Bellingshausen and Edward Bransfield reported sighting land earlier in 1820, Palmer was the captain of the third vessel, the Hero, to sight the continent of Antarctica, and actually set foot on land. Palmer also helped discover the nearby South Orkney Islands archipelago.
After concluding a successful sealing career, Palmer, still in the prime of life, switched his attention to the captaining of fast sailing ships for the transportation of express freight. In this new role, the Connecticut captain traveled many of the world's principal sailing routes. Observing the strengths and weaknesses of the ocean-going sailing ships of his time, Palmer suggested and designed improvements to their hulls and rigging. The improvements made Palmer a co-developer of the mid-1800s clipper ship.
Palmer closed his sailing career and established himself in his hometown of Stonington as a successful owner of clipper ships sailed by others. He died in 1877, aged 78. Palmer Land, part of the Antarctic Peninsula, as well as the Palmer Archipelago, were named in his honor.
The Antarctic science and research program operated by the U.S. government continues to recall Palmer's role in the exploration of the Antarctic area. Palmer Station, located in the seal islands that Palmer explored, and the Antarctic icebreaker RV Nathaniel B. Palmer are named after Captain Palmer. His home in Stonington, the Capt. Nathaniel B. Palmer House, was declared a National Historic Landmark in 1996.