Shelton was born and raised in her family's home of thirteen rooms in Rural Plains, in Hanover County, Virginia. In 1754 at age sixteen, Sarah and Patrick were married. Almost a year later, Sarah gave birth to her first child Martha and by 1771, the couple had six children together.
Sarah Shelton started to show signs of mental illness after the birth of her last child, Edward (whom many called Neddy). Patrick Henry's mother sent a letter to his sister which stated, "We feel Sarah is losing her mind after the birth of little Neddy". We know today that she was probably suffering from postpartum depression or puerperal psychosis. It is unknown when Sarah's private doctor strongly suggested that she be sent to the new Eastern State Hospital in Williamsburg, Virginia. However, her husband disagreed and did not want to send her to an asylum. He likely wanted to keep her home due to the horrible conditions and treatments. Patrick was politically active when he decided to keep his wife in confinement in the cellar of their home. Because of her husband's money and resources, she was able to avoid suffering the consequences of the poor laws.
It was said that her behavior was so unmanageable that "she was confined in a cellar room, bound in a straightjacket, and attended by a servant." According to research, it is believed that a female slave took care of Sarah in the cellar. There are very few documents about the confinement of Sarah likely due to the fact that her husband became the governor of Virginia and this secret was kept from society. After three or four years in confinement, Sarah died in the spring of 1775. Although the precise location of her burial is unknown, it is believed that her grave is thirty feet from the cellar door.