Calamity Jane was born on May 1, 1852, as Martha Jane Cannary in Princeton, within Mercer County, Missouri. Her father was a gambler. Little is known about her mother.

At age 14, Martha Jane took charge of her five younger siblings, loaded up the family wagon and set out for Wyoming Territory. She took whatever jobs she could to provide for her large family, working as a dishwasher, cook, waitress, dance hall girl, nurse, and ox team driver.

In The Life and Adventures of Calamity Jane, Calamity herself explains: "It was on Goose Creek, Wyoming where the town of Sheridan is now located. Capt. Egan was in command of the Post. We were ordered out to quell an uprising of the Indians, and were out for several days, had numerous skirmishes during which six of the soldiers were killed and several severely wounded. When on returning to the Post we were ambushed about a mile and a half from our destination. When fired upon, Capt. Egan was shot. I was riding in advance and on hearing the firing turned in my saddle and saw the Captain reeling in his saddle as though about to fall. I turned my horse and galloped back with all haste to his side and got there in time to catch him as he was falling. I lifted him onto my horse in front of me and succeeded in getting him safely to the Fort. Capt. Egan, on recovering, laughingly said: 'I name you Calamity Jane, the heroine of the plains.' I have borne that name up to the present time."

In 1876, Calamity Jane settled in the area of Deadwood, South Dakota, in the Black Hills. There she became friends with Dora DuFran, the Black Hills' leading madam, and was occasionally employed by her. She also rubbed shoulders with the likes of Wild Bill Hickok and caught the attention of dime novel writer Edward Wheeler, who worked Calamity Jane into his popular stories as a Wild West heroine.

Accounts say that she stood around six-feet tall, with brown hair and had a heavy bone structure. She was also known for wearing men's attire, which added to her masculine appearance.

At one point, she helped save numerous passengers in an overland stagecoach by diverting several Plains Indians who were in pursuit of the vehicle. Stagecoach driver John Slaughter was killed during the pursuit, and Jane took over the reins and drove the stage on to its destination at Deadwood.

When smallpox ravaged Deadwood in 1878, Jane cared for eight afflicted gold miners. One man described her as "the last person to hold the head of and administer consolation to the troubled gambler or erstwhile bad man who was about to depart into the new country."

Calamity Jane later claimed she was so upset by Hickok's murder that she went after his killer with a meat cleaver, having left her guns at her residence. According to historical accounts, however, this story is more fiction than fact.

After the death of Wild Bill, Jane moved around and even joined Buffalo Bill's Wild West show, performing her sharpshooting act astride a galloping horse.

In the late 1880s, Jane returned to Deadwood with a child who she claimed was her daughter. At Jane's request, a benefit was held in one of the theaters to raise money for her daughter's education in St. Martin's Academy at Sturgis, South Dakota, a nearby Catholic boarding school. The benefit raised a large sum. Jane got drunk, spent a considerable portion of the money that same night, and left with the child the next day.