Prudence Crandall was born on September 3, 1803, to Pardon and Esther Carpenter Crandall, a Quaker couple in the Hope Valley area in the town of Hopkinton, Rhode Island. When she was 17, her Father moved the family to Canterbury, Connecticut. In Providence, Rhode Island, Crandall attended Friends' Boarding School. After graduating, Prudence Crandall taught a school in the nearby town of Plainfield, Rhode Island.

In 1831, she purchased a house, with her sister Almira Crandall, to establish the Canterbury Female Boarding School, at the request of Canterbury's aristocratic residents, to educate young girls in the town. With the help of her sister and a maid, she taught about forty children in different subjects including geography, history, grammar, arithmetic, reading, and writing. As principal of the female boarding school, Prudence Crandall was deemed successful in her ability to educate young girls, and the school flourished until September 1832.

Prudence Crandall's chance to help people of color came in the fall of 1832. Sarah Harris, the daughter of a free African-American farmer near Canterbury, asked to be accepted to the school to prepare for teaching other African Americans.

Arthur Tappan of New York, a prominent abolitionist, donated $10,000 to hire the best lawyers to defend Crandall throughout her trials. The first opened at the Windham County Court on August 23, 1833. The case challenged the constitutionality of the Connecticut law prohibiting the education of African Americans from outside the state.

In August 1834, Prudence Crandall married the Rev. Calvin Philleo, a Baptist preacher in Canterbury, Connecticut. The couple moved to Massachusetts for a period of time after they fled the town of Canterbury, and they also lived in New York, Rhode Island, and Illinois. It was later, in Illinois, that Rev. Calvin Philleo died in 1874.

Other members of the family had difficulty with authorities during the 1830s. In May 1835, their brother, Reuben Crandall, who had studied Medicine at Yale and taught botany, had moved from Peekskill, New York to Washington, D.C. He received a medical license there, and began giving lectures and cataloging plants. His trunks held many Anti-Slavery Society tracts and newspapers (some of which he used to wrap plants). On August 10, 1835, two constables arrested him on the charge of possession of abolitionist tracts with the intent to distribute them. A lynch mob gathered at the jail and U.S. Attorney Francis Scott Key prosecuted him. This was a short time after rioting by whites against blacks that had followed the alleged attempted murder of a white woman by a mentally ill slave, Arthur Bowen. Crandall was jailed for eight months before the two-week trial, but the jury acquitted him of all five charges. However, Crandall had contracted tuberculosis (TB), which had no known treatment. After returning briefly to Connecticut, he moved in 1836 to the milder climate of Jamaica in the Caribbean, where he died of the disease, at age 30.

Connecticut officially repealed the Black Law in 1838.

After the death of her husband, Crandall relocated with her brother Hezekiah to Elk Falls, Kansas around 1877, and it was there that her brother eventually died in 1881. In 1886, the state of Connecticut honored Prudence Crandall with an act by the legislature, prominently supported by Writer Mark Twain, providing her with a $400 annual pension (equivalent to $10,900 in 2017). Prudence Crandall died in Kansas on January 28, 1890, at the age of 86. She and her brother Hezekiah are buried in Elk Falls Cemetery.

Under the Black Law, the townspeople refused any amenities to the students or Crandall, closing their shops and meeting houses to them. Stage drivers refused to provide them with transportation, and the town doctors refused to treat them. Townspeople poisoned the school's well—its only water source—with animal feces, and prevented Crandall from obtaining water from other sources. Not only did Crandall and her students receive backlash, her Father was insulted and threatened by the citizens of Canterbury. Although she faced extreme difficulties, Crandall continued to teach the young women of color which angered the community even further.