Sipprell's father died before Clara Estelle Sipprell was born in Tillsonburg, Ontario, Canada. In 1895, she and her mother moved from Canada to Buffalo, New York, where several of her five older brothers had established themselves. She was introduced to photography in the portrait studio of her brother Francis James, where she later worked as an assistant and ultimately became a partner in the business.

Clara became one of the foremost practitioners of pictorial photography in the United States. As a portrait photographer, Clara sought to convey a sense of the whole person and what made each unique. She also photographed landscapes, still lifes, female nudes, major individuals in the arts and government, and people in the countries in which she traveled.

In 1915, Clara, then thirty, moved to New York City with Jessica E. Beers, with whom she lived until 1923. She opened a photographic studio in Greenwich Village and eventually became a contract photographer for the Ethical Culture School, where Beers was a principal.

A Russian immigrant, Irina Khrabroff, was first her student and later her traveling companion, close friend, and business manager. As a student, Khrabroff spent her winters living with Clara and Beers in New York City. In 1923, when Khrabroff married, Beers moved out of the apartment, but Clara continued living there with Khrabroff and her husband until 1933.

Around 1937, Phyllis Fenner - a writer, librarian, and anthologist of children's books -became Clara's housemate and traveling companion. This relationship continued through the final thirty-eight years of Clara's life. In the mid-1960s, they had Harold Olmstead build them a house in Manchester, Vermont.

Clara died at the age of eighty-nine. Her ashes are buried in a plot near an outcropping of rock in Manchester. Attached to the rock is a small bronze tablet on which, in accordance with her wishes, are engraved her own name along with the names of Jessica Beers and Phyllis Fenner.

It is not clear whether or not Sipprell's relationships were sexual or even romantic, yet their length and stability, and the evidence of the memorial marker, indicate an extraordinary level of commitment.