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Family and early life
Born in 1881 in Memphis, Tennessee, into a prominent family, Mary Breckinridge was a daughter of Arkansas Congressman, US Minister to Russia Clifton Rodes Breckinridge and a granddaughter of Vice President John C. Breckinridge. Though born into a prominent family with means, she looked on as the males in her family received a higher quality education than was afforded to her. Nevertheless, she was educated by private tutors in Washington, D.C., Switzerland and in St. Petersburg, Russia. She obtained a degree from St Lukes Hospital New York in Nursing in 1910 and advanced Midwife Training at a Hospital in London, England. In 1894, Breckinridge and her family moved to Russia when President Grover Cleveland appointed her father to serve as the U.S. minister to that country. They returned to the United States in 1897.

Breckinridge entered a world where the primary roles of women were wife and mother, yet her legacy as the founder of the Frontier Nursing Service has reached more lives than the contributions of the men in her family. Breckinridge's mother disapproved of her cousin Sophonisba Breckinridge's going to college and starting a career. She helped to ensure that her daughter followed a more traditional path. Breckinridge was married in 1904 to a lawyer, Henry Ruffner Morrison, of Hot Springs, Arkansas. He died only two years later; the couple had no children.

As a young widow, Breckinridge entered a nursing class at New York City's St. Luke's Hospital. She remained there three years, taking a degree in nursing in 1910 before returning to the South.

In 1912 she married Richard Ryan Thompson, a Kentucky native who was serving as the president of Crescent College and Conservatory in Eureka Springs, Arkansas. The couple had two children. Their daughter Polly was born prematurely in 1916 and did not survive. Two years later, their beloved four-year-old son, Clifford Breckinridge ("Breckie") Thompson, died of appendicitis. Breckinridge's husband was unfaithful; they were divorced in 1920 and Breckinridge resumed the use of her maiden name.

Life's tragedies called her to adventure, as "a touring speaker with the U.S. Children's Bureau and as a relief worker in France after WWI.