Penelope Padgett was born in Edenton, North Carolina in 1728. The daughter of a prominent doctor, she married attorney John Hodgson in 1745 after Hodgson's former wife, (and Penelope's older sister) Elizabeth died. Penelope assumed the care of her three nieces and nephews and also had two children of her own before John Hodgson's death in 1747.

Widowed at age nineteen with five children under her care, Penelope's extended family split the care of the Hodgson children and Penelope soon married again, this time to planter James Craven in 1751. He died in 1755, leaving Penelope not only with the Hodgson plantation, but also the entirety of the Craven estate as well.

Penelope married her third and final husband, noted attorney and politician Thomas Barker, in 1757. In 1761 Thomas Barker left Penelope in Edenton to manage their property while he went to England to assume his new role as agent for the colony of North Carolina. Though they did not know it at the time, Barker would not return to North Carolina until 1778.

In October 1774 Penelope Barker played an important role in in organizing a group of local women to sign a nonimportation agreement which later became known as the Edenton Tea Party Resolves. After the resolves, Penelope Barker continued to live in Edenton, where she was a staunch advocate for the Patriot cause. She died in 1796.