He learned line engraving, and produced several of the plates in William Young Ottley's Early Florentine School (1826).

For about ten years after his arrival in the United States, he painted portraits in oil and miniatures on ivory.

During the same time, he found employment in making designs for banknote vignettes, and also in drawing on wood for book illustrations.

He had an interest at the same time in the Eclectic Museum, for which, later, when John H. Agnew was alone in charge, he simply engraved the plates.

During this time, besides his editorial work and the engravings that had to be made regularly for the periodicals with which he was connected, Sartain produced an enormous quantity of plates for book-illustration.

Around July 2, 1849, about four months before Poe's death, the author unexpectedly visited Sartain's house in Philadelphia.

He held various offices in the Artists' Fund Society, the School of Design for Women, and the Pennsylvania Academy of Fine Arts, and was actively connected with other educational institutions in the city.

His architectural knowledge was frequently requisitioned: he took a prominent part in the work of the committee on the Washington Memorial by Rudolf Siemering in Fairmount Park, Philadelphia, and he designed medallions for the monument to George Washington and Lafayette erected in 1869 in Monument Cemetery, Philadelphia.

[9] Shortly before his death, The Philadelphia School of Design for Women created the John Sartain Fellowship in recognition of his 28 year tenure as Director.

In 1877, he returned to the United States, settling in New York, where he was elected an associate of the National Academy of Design in 1880.