Jessie Benton was the daughter of Senator Thomas Hart Benton (Benton, Thomas Hart) of Missouri. She was well educated, mainly privately, and was notably independent and spirited. In 1840 she met Lieutenant John C. Frémont (Frémont, John C), a young officer in the Topographical Corps, and in 1841, over her father's strong opposition, they were secretly married. Senator Benton chose to make the best of it and began using his considerable influence to further his son-in-law's career as an explorer.

While her husband was on his first expedition to the Wind River country, Jessie Frémont served as her father's hostess and occasionally translated secret Spanish documents for the State Department. As her husband prepared to leave on his second expedition in 1843, she intercepted and suppressed an order from Washington, D.C., that she feared threatened his command. She urged him to leave at once and then wrote to authorities in Washington explaining what she had done. She was largely responsible for the literary quality of the 1844 report on his second expedition; it was printed as a Senate document in an edition of 10,000 copies and widely sold in a commercial edition as well. In 1849, following her husband's third expedition, his controversial role in the conquest of California, and his court-martial, she sailed to San Francisco to join him.

After about 1851 the Frémonts grew wealthy. Jessie Frémont took what little part custom allowed in her husband's presidential campaign in 1856, and afterward they returned to California. She was, as ever, her husband's most loyal partisan in his troubled Civil War service, first as commander of the Western Department in St. Louis, Missouri, and later in field command in Virginia. The Story of the Guard: A Chronicle of the War (1863) reprinted her articles in the Atlantic Monthly defending him. After her husband's bankruptcy in 1873, she took up writing with a will. Articles, memoirs, travel sketches, and stories appeared in leading magazines. Many of them were collected in such books as A Year of American Travel (1878) and Far-West Sketches (1890). She was also the principal author of her husband's Memoirs of My Life (1887).