Greenhow was born as Maria Rosatta O'Neale, and was orphaned as a child. As a teenager O'Neal moved from her family's Maryland farm to her aunt's fashionable boardinghouse in Washington, D.C. Personable, intelligent, and outgoing, she adapted easily to the social scene of the capital, and people in Washington's highest circles opened their doors to her. As a young woman, Greenhow was considered beautiful, educated, loyal, ambitious, compassionate, and refined. She disappointed an army of suitors by marrying Dr. Robert Greenhow. Dr. Greenhow served as her mentor during the early part of their marriage.
The Greenhows welcomed four daughters into their family: Florence, Gertrude, Leila, and little Rose. Eventually, tragedy struck the family. Dr. Greenhow died soon after little Rose's birth. After Dr. Greenhow's death, Greenhow saw her oldest child Florence move west, and later, just prior to the Civil War, her daughter Gertrude died. Greenhow's sympathy for the Confederate cause grew after her husband's death. She was strongly influenced in her commitment to the right to secession by her friendship with John C. Calhoun. Greenhow's loyalty to the Confederate cause was noted by those with similar sympathies in Washington, and she was soon recruited as a spy.
Among her friends were presidents, senators, high-ranking military officers, and less important people from all walks of life, many of whom played knowing or unknowing roles in the espionage ring she organized in 1861. She used her connections to pass along key military information to the South at the start of the war. One of her closest companions had been Calhoun, whose political instruction sealed her identification with and loyalty to Southern interests.
A widow when war broke out, Greenhow immediately used her contacts and talents to provide Gen. P.G.T. Beauregard with critical information resulting in the Confederate victory at 1st Bull Run. President Jefferson Davis credited Greenhow's information with securing victory at Manassas for the South.
Knowing that many in Washington suspected her of spying for the Confederacy, Greenhow feared for her remaining family's safety, and she soon sent her daughter Leila to France. Allan Pinkerton, head of the recently-formed Secret Service, was suspicious as well. On August 23, 1861, Pinkerton apprehended Greenhow, placing her under house arrest. Other leaked information was traced back to Greenhow's home, and upon searching her home for further evidence, Pinkerton and his men found maps of Washington fortifications and notes on military movements.
On January 18, 1862, Greenhow and her eight-year-old daughter Rose were incarcerated in the Old Capitol Prison. While in prison, Greenhow's daughter was permitted to remain with her. Greenhow was said to have continued to pass along messages while in unusual ways. For example, she was said to have sent one message concealed within a woman visitor's bun of hair. News of her activities brought publicity and tremendous popularity among Southern sympathizers. After being brought to trial in spring 1862, Greenhow was deported to Richmond, where cheering crowds greeted her.
Davis welcomed Greenhow home, and soon, he enlisted her as a courier to Europe. From 1863 - 1864, Greenhow traveled through France and Britain on a diplomatic mission for the Confederacy. There was much sympathy for the South among European aristocrats. While in France, Greenhow was received in the court of Napoleon III. In Britain, she had an audience with Queen Victoria. Two months after arriving in London, she wrote her memoirs, "My Imprisonment", and the details of her mission to Europe are recorded in her personal diaries, dated August 5, 1863 through August 10, 1864.
In September 1864, Greenhow left Europe to return to the South, carrying dispatches. She traveled on the Condor, a British blockade runner. On October 1, 1864, the Condor ran aground at the mouth of the Cape Fear River near Wilmington, North Carolina. A Union gunboat, USS Niphon, had been pursuing the ship. Fearing capture and reimprisonment, Greenhow fled the grounded Condor by rowboat. The rowboat did not make it to shore, however; it was capsized by a wave, and Greenhow, weighed down with $2,000.00 worth of gold intended for the Confederate treasury, drowned. Her body was found and identified a few days later and buried with honors in Wilmington.
In October of 1864, Greenhow received a full military burial in Oakdale Cemetery, Wilmington, North Carolina. Her coffin was wrapped in the Confederate flag, and she was widely regarded as a soldier and a heroine.