Peale came from an artistic legacy: her father, James Peale, was a painter remembered for his still lifes, and her uncle Charles Willson Peale (Peale, Charles Willson) was a well-known portraitist and museum entrepreneur. She sold her first paintings (copies) at age 14, and in 1811 she exhibited a still life of fruit at the first exhibition of the Pennsylvania Academy of the Fine Arts, Philadelphia. Three years later she showed a group of three miniatures there. In 1818–19 she traveled to Washington, D.C., to enter the studio of her uncle Charles and won his highest praise for her miniature portraits on ivory. Her sympathetic portraits, heightened by contrasting backgrounds and a remarkable attention to detail, brought her more commissions than she could comfortably handle. Among her subjects were prominent statesmen of the new republic, including James Monroe (Monroe, James), Andrew Jackson (Jackson, Andrew), Henry Clay (Clay, Henry), and William Bainbridge (Bainbridge, William). In 1824 she was elected to the Pennsylvania Academy, where she continued to exhibit regularly until 1842. She married in 1829 but was a widow within a few brief months. She retired from painting in 1841, following her second marriage, to Gen. William Duncan.