We report the first record of invasive Orconectes rusticus (Rusty Crayfish) in the Potomac River, MD. Four specimens were collected in June 2010 in the Potomac River downstream from the confluence of Antietam Creek near Sharpsburg, MD. Subsequent surveys in the Potomac River mainstem and three other tributaries from Brunswick to Hancock, MD indicate that this invasive species is not yet widespread in the river. Further spread of Rusty Crayfish in the Potomac River may displace congeneric species including two natives, Orconectes obscurus (Allegheny Crayfish) and Orconectes limosus (Spinycheek Crayfish), and the non-native Orconectes virilis (Virile Crayfish) in Maryland, Virginia, and West Virginia.