Fannie Nampeyo was born in the Corn Clan home of her mother, Nampeyo of Hano, around 1900. She was the youngest daughter born to Nampeyo and Lesou. The older women of her father's family gave her the name Popongua or Popong-Mana, which means "Picking Pinons." It has been said the name "Fannie" was given to her by either missionaries or health care workers on the Hopi Reservation.

Fannie attended the Polacca Day School, completing her formal education when she graduated from third grade. While many young girls in the Hano-Tewa Village area of Hopi grew up learning how to make pottery alongside their mothers, Fannie didn't. In her teens she worked at the Hubbell Trading Post as a maid and contributed to her family income that way. She has been referred to as "tempestuous" in those days, and least compatible with her mother. It wasn't until after she married Vinton Polacca in the early 1920s that she began to be interested in making pottery. That was also about the same time her mother was losing her eyesight due to untreatable trachoma. Fannie worked with Nampeyo more and more, learning how to polish from her father and how to paint from her mother. In those years, if they signed their pottery the signature was simply "Nampeyo," and as Nampeyo herself never learned to read or write, Fannie most likely did all the signing. Later pieces they collaborated on she signed "Nampeyo Fannie" while pieces Fannie made by herself she signed "Fannie Nampeyo" and usually included a Corn Clan symbol.

From the early 1920s until she passed on in 1987, Fannie was an outstanding and prolific potter. She most often made jars, cups, saucers, miniatures and bird effigy bowls. Her favorite styles were red-and-black-on-yellow and black-on-yellow. Her favorite designs appear to have been the favorite designs of her mother: bird elements, clouds, stars and migration patterns.

After her mother passed on, Fannie became the Matriarch of the Hopi-Tewa Corn Clan, as her mother had been. Fannie didn't just make pottery either: she developed a successful tamale business in Keams Canyon and she also made quilts. Fannie taught all of her children how to make pottery and several of them excelled at it. All of her children graduated from high school and most went on to college or university.