The Appoquinimink River is a river flowing to Delaware Bay in northern Delaware in the United States. The river is 15.3 miles (24.6 km) long and drains an area of 47 square miles (120 km) on the Atlantic Coastal Plain.

The Appoquinimink flows for its entire length in southern New Castle County. It rises approximately 2 miles (3 km) west of Townsend and flows generally eastwardly, south of Middletown and past Odessa, to its mouth at the northern end of Delaware Bay, approximately 3 miles (5 km) east of Odessa. In its upper course the river passes through two man-made lakes, Wiggins Mill Pond and Noxontown Lake; the river is tidal to the dam at Noxontown Lake, and salinity from Delaware Bay typically affects the lowermost 5 miles (8 km) of the river. The lower 7 miles (11 km) of the river are considered to be navigable by the U.S. Army Corps of Engineers.

It collects three named tributaries along its course: From the north, Deep Creek, 4.2 miles (6.8 km) long (also known historically as the "North Appoquinimink River"); and Drawyers Creek, 8.2 miles (13.2 km) long; and from the south, Hangmans Run.

According to 2002 data from the United States Environmental Protection Agency, 54.9% of the Appoquinimink River watershed is occupied by agricultural uses (predominantly soybeans, corn, and wheat); 15.1% is residential; 9.9% is wetland; and 8.8% is forested.

In 2004, a non-profit group, The Appoquinimink River Association, was founded with a mission to protect the water and natural resources in the region surrounding the Appoquinimink River.

The United States Board on Geographic Names issued a decision clarifying the stream's name in 1950. According to the Geographic Names Information System, the Appoquinimink River has also been known historically as:

Apequinemy River Apoquemene Creek Apoquiminy Creek Apoquin Creek Apoquinemy Creek Apoquinimune Creek Apoqunimy Creek Appaquinimink Creek

Appoquenema Kill Appoquenimi Creeke Appoquinimink Creek Appoquinimunk Creek Appquenemink Creek Drawyer Creek Minques Kil

Minques Kill Opoquenin Creek Opoquimony Creek Opoquimorn Creek Oppequimina Creek Oppoquenmin Creek Oppoquenmink River

• List of Delaware rivers
• List of Delaware River tributaries

• North Carolina State University: Appoquinimink River basin project
• Appoquinimink River Association