A world record for Southwest American Indian pottery was declared at Bonhams Auction House in San Francisco on December 6, 2010, when one of Nampeyo's art works, a decorated ceramic pot, sold for $350,000.

[5] Her mother, White Corn was Tewa; her father Quootsva, from nearby Walpi, was a member of the Snake clan of the Hopi Nation.

Her grandmother, a member of the Snake clan, named the baby Tcu-mana, or snake-girl in the Hopi language.

Nampeyo may have learned Hopi pottery making through the efforts of her father's mother, though her biographer Barbara Kramer believes this theory implausible.

In the 1870s, Nampeyo made a steady income by selling her work at a local trading post operated by Thomas Keam.

Lesou, her husband, was reputedly employed by the archaeologist J. Walter Fewkes at the excavation of the ancient ruins of the Hopi village Sikyátki on the First Mesa in the 1890s.

[9][5] However, she began making copies of protohistoric pottery from the 15th through 17th centuries from ancient village sites,[6] such as Sikyátki, which was explored before Fewkes and Thomas Varker Keam.

[22] Between 1905 and 1907, she produced and sold pottery out of a pueblo-like structure called Hopi House, a tourist attraction (combination of museum, curio shop, theatre, and living space for Native American dancers and artists) at the Grand Canyon lodge, operated by the Fred Harvey Company.

An example is a 1930s vase in the collection of the Smithsonian Institution's National Museum of the American Indian in Washington, D.C.[18] Her work is distinguished by the shapes of the pottery and the designs.

[22] She inspired dozens of family members over several generations to make pottery, including daughters Fannie Nampeyo and Annie Healing.

[9][24] A 2014 exhibit at the Museum of Northern Arizona presents the works of four generations of artists descended from Nampeyo.