The stamp designs feature historic moments in U.S. postal history and depict objects and themes represented in the museum's inaugural exhibit galleries.

According to the museum's founding director, James H. Bruns, the National Postal Museum helped determine which objects and images would be used in the design. Many of the elements depicted in the stamps were represented in the museum's inaugural displays - including a Concord stage coach, a 1930s mail truck, and the Inverted Jenny stamp. Bruns said the "stamps were, in effect, like a miniature visit to the Museum." The stamps are "semi-jumbo" (a little larger than usual). The complex designs feature portraits and line drawings. The main figures are framed by a circular white background.

The stamp depicting the 18th century features Benjamin Franklin, reflecting his career as printer, postmaster and statesmen. He is represented by a printing press, mail rider, and Independence Hall. The Franklin portrait is based on the well-known painting by Joseph-Siffred Duplessis which can be found in the Smithsonian's National Portrait Gallery.

A Civil War soldier, Concord stagecoach, and pony express rider embody the 19th century. The 20th century is represented by airmail pilot Charles Lindbergh, a railway mail car, a 1931 Model A Ford mail truck, and JN-4H "Jenny" bi-plane. The fourth stamp features the art of letter writing, using memorable words from a California gold rush letter; four prized U.S stamps (90¢ George Washington, 2¢ Empire State Express, 24¢ Inverted Jenny, and 65¢ Graf Zeppelin), an undated postmark from Milledgeville, Georgia and a barcode representing contemporary mail processing technology.