It separates Sinepuxent Neck, in Worcester County, Maryland from Assateague Island, and West Ocean City, Maryland from downtown Ocean City.

Historically the area was referred to by various names including Sinepuxent, Sene Puxon, Synepuxent, Cinnepuxon, et al.[2] Sinepuxent Inlet, a navigable waterway through the barrier island during the colonial era, was located just south of the Assateague Island National Seashore day-use area.

In September 1698 French pirate Canoot seized a Philadelphia-based sloop "as he was coming out of Cinnepuxon Inlet.

[2] Sinepuxent was a once-thriving community on the mainland about a half mile north of the Verrazano Bridge, also destroyed in the same hurricane.

The new inlet was stabilized by rock jetties constructed by the United States Army Corps of Engineers, with work commencing in October 1933.