George Zettlein (July 12, 1844 – May 22, 1905) was an American professional baseball pitcher.

He played six seasons in Major League Baseball from 1871 to 1876 for the Chicago White Stockings, Troy Haymakers, Brooklyn Eckfords, Philadelphia White Stockings of the National Association (NA), and the Philadelphia Athletics (1860–1876) of the National League.

He began playing baseball in 1865 for Eckford of Brooklyn in the National Association of Base Ball Players, the amateur-only predecessor to the NA.

In 1871, Zettlein joined the professional White Stockings of the NA, and in May 1871 he gave up the new league's first home run.

[1] The following season, Zettlein played for the Troy Haymakers and Brooklyn Eckfords, combining for 15 wins and 16 losses between the two teams.