Alfred Thompson trained as a lawyer but turned to painting shortly before the Civil War, painting both landscapes and portraits. He studied in Baltimore and in Paris. He studied with Gleyke in 1861 to 1862 and also with E. Lambinet and A. Pasisi in the period 1862 to 1868.
He served as an illustrator of war scenes with Harper’s Weekly and Illustrated London News for the first year of the Civil War. In 1861 he went to Paris for further study and returned to the United States in 1868, the same year he exhibited at the Pennsylvania Academy of the Fine Arts. He exhibited at the National Academy of Design from 1867 until his death and was elected an associate (A.N.A) in 1873 and an academician (N.A.) in 1875.
Thompson had a studio in New York City from 1868. In 1876 one of his paintings was exhibited at the Leonard Auction Rooms in Boston.
He traveled often throughout Europe and the United States during his career, searching for material to draw.