As an American painter, Peale's work was characterized by its attention to detail and naturalistic approach. His artwork frequently featured subjects from history, mythology, and everyday life. Peale's signature style often incorporated elements of neoclassicism and romanticism, reflecting his European influences.

Peale's artistic career spanned over seven decades, during which he created numerous notable works. One of his most famous paintings is the portrait of George Washington, which he created from a 1784 portrait by Charles Willson Peale. This artwork showcases the artist's skill in capturing the likeness and personality of his subjects.

Throughout his life, Rembrandt Peale exhibited his work at various exhibitions, including the Pennsylvania Academy of Fine Arts. His contributions to American art were significant, as he helped establish the country's artistic identity. Today, Peale's artwork can be found in institutions such as the National Gallery of Art and the Philadelphia Museum of Art.