Rembrandt Peale shares a birthday with George Washington and is a son of a well-known artist, Charles Willson Peale, suggesting that he had a certain fate shaped out for him at birth. Peale was born on February 22, 1778, on the VanArtsdalen farm near Richboro, Bucks County, but spent most of his life in Philadelphia, Pennsylvania. He was the third child of Rachel Brewer and Charles Willson Peale. He grew up in a happy and affectionate family that believed in the goals of improvement and responsibility. By growing up in the presence of a great painter such as Charles Willson Peale, Rembrandt Peale was seemingly bound to a painting career. Peale was tutored by his father in art and the natural sciences, lectured on having a healthy mind, and given moral instruction.

He began to draw at the age of eight, and by age 13 he had produced his first self-portrait. As a dedicated and ambitious child, he did the best he could to apply himself to the study of art and spoke of the great pleasure he took in the collection of his father's engravings. By the time Peale was 16, his father was promoting him and his brother, Raphael, in the newspapers, while also announcing that he was retiring from painting. At one point in his life, Rembrandt Peale studied the chemistry of paint at the Medical College of the University of Pennsylvania, developing the coloring system that amazed his father more and more with every painting. His father looked out for his career and his well-being his whole life. In 1795, Charles arranged for Rembrandt Peale to paint a portrait of President Washington. He found the project so fascinating that he made multiple copies of the painting and would conduct numerous speaking tours on the subject of Washington's portraits.

In 1796, Raphael and Rembrandt Peale opened the first Peale Museum in Baltimore, Maryland. In order to continue his studies of art, Rembrandt Peale left the museum for Europe. Traveling through France, England, and Italy did not seem to satisfy his hunger for art, so in 1800 he came back to Philadelphia to open his own "painting room." He also tried to advertise in American Daily Advertiser, to set himself apart from the rest of the Peales. However, when that did not work, Rembrandt Peale was sent to England to earn some money for the study of the mastodon skeleton. In the period from 1802 to 1803, he studied with another great artist, Benjamin West, at the Royal Academy. Still unable to satisfy his artistic longings, he left for Paris where he studied history paintings. In February 1806, Charles Willson Peale wrote to his daughter, Angelica: "Rembrandt is very successful, his portraits give universal satisfaction, he cannot execute fast enough for the demand, and he is not wanting industry in consequence he is beginning to raise his price for portraits."

In 1810, Rembrandt Peale no longer had the desire to paint portraits. He felt like he was wasting time on portrait painting when he devoted his efforts to historical paintings. First, he joined other artists of Philadelphia to support the Society of Artists, and then he opened the picture gallery for the exhibition of history paintings called the Apollodorian Gallery of Paintings. In this gallery he created two of his major paintings: Napoleon and The Roman Daughter, as well as the biblical piece The Ascent of Elijah. However, Philadelphia was not ready for such art and some critics even said that he would be better off with portrait paintings. Crushed, Peale moved the gallery to Baltimore, Maryland, in 1814, hoping for a more enthusiastic response. The Baltimore Museum was not a great of success, largely due to the War of 1812 that came to Baltimore. This left him crushed and devastated because no one was in the mood to go to museums. To solve the financial problems, Peale sent his large moral painting The Court of Death out into the country on exhibit, but that did not help him much. He ended up selling his museum in Baltimore to his brother, Rubens, where he found himself in debt.

Rembrandt began going back and forth between New York and Boston in order to find a community that would respect his art. In New York, he became a founding member of the National Academy of Design; in Boston, he experimented with lithography. In 1828, he borrowed money and left for Europe again to open a studio in London. Even though he created some interesting and important art there, it did not seem to work out for him, so he came back to America. In New York, Peale became a president of the American Academy of Fine Arts.

In 1830, Rembrandt Peale permanently settled in Philadelphia, where he published some of his textual work, including: Notes on Italy, Graphics, Portfolio of an Artist, and articles in The Crayon. His Graphics was particularly influential in the teaching of artistic principles to the lay public. He also started teaching writing and drawing as well as giving lectures on paintings of Washington at the Central High School in Philadelphia. He gave up the teaching job in 1840, and he devoted himself to painting, regretting the time he lost from not painting.

Peale died in his house at 1506 Vine Street in Philadelphia, Pennsylvania, on October 3, 1860. Reports at the time said, "the disease which carried him off was dropsy of the heart."