Flora Vesta Knisely was born on 23 April 1863, the eldest of six children. Her family were of German ancestry who had moved to Pennsylvania. When Flo was ten years old, her father died of cancer, leaving his family impoverished. Flo's mother Amanda, rather than allowing her family to be broken up and her children sent to live with family friends, moved the family to Industry, Kansas (not far from Abilene), and began working her own farm. Flo raised her younger siblings from an early age.

Following in her mother's footsteps, Flo took up the cause of prohibition. She taught in Clay Center to help raise family income, and while teaching roomed with a woman who was trained in medicine. After this, Flo enrolled for classes at Campbell College in Holton, KS.

While Flo was attending classes, Charles Frederick Menninger was teaching at Campbell. Menninger began joining Flo and her brother Elmer in their rooms to study, and in January 1885 Charles and Flo married. Thereafter, C.F. began studying medicine in Chicago, and Flo continued teaching in Holton. Eventually the couple moved to Topeka, where C.F. opened his medical practice and Flo continued teaching until the birth of her first child.

The couple had three children in the 1890s: Karl, Edwin, and William Claire. In 1898 Flo began organizing a Bible study class for any woman in Topeka, after the class she had been attending became exclusive to unmarried women. She developed an extensive outline for a four-year course, which became the basis for both her in-person classes and for long-distance courses for women requesting to study from the outline. Eventually Flo's Bible studies course was taught nationwide in Young Women Christian Associations (YWCAs).

The Bible course remained a central part of Flo's identity for the rest of her life. In 1939, with the help and urging of her sons, Flo published an autobiography focusing on her early life, entitled Days of My Life. Flo Vesta Knisely Menninger died on 9 February 1945.

[Information retrieved from biographical sketch for Papers of Flora V. Menninger, Kansas Historical Society, https://www.kshs.org/camp/units/view/225923.]