Raphaelle Peale began his artistic work in the family enterprise led by Charles Willson Peale, collaborating on portraits and assisting with museum activities. In 1792 he traveled to South America to collect specimens for the Philadelphia museum. He exhibited portraits and other paintings at Philadelphia's Columbianum in 1794, then joined his brother Rembrandt in efforts to establish a museum in Baltimore. These ventures mixed art, natural history and commercial display.

After 1800 Peale earned money through miniatures, silhouettes and a profile-making machine known as the physiognotrace. From about 1810 he concentrated increasingly on still-life painting, showing his work frequently at the Pennsylvania Academy of the Fine Arts. Fruit, cakes, vegetables, glass and tableware became subjects for precise arrangements of light, color and texture. Still life offered fewer commissions and less prestige than portraiture, which his father urged him to pursue.

His paintings also explored visual deception. In Venus Rising from the Sea—A Deception, a painted cloth appears to conceal a bathing woman, drawing on the classical contest between painters Zeuxis and Parrhasius. Illness, gout and heavy drinking restricted his mobility and disrupted his work, and he often relied financially on his father. He nevertheless produced the concentrated body of still lifes for which he is remembered before his death in Philadelphia in 1825, establishing still life as an American specialty.