Colonia del Sacramento (formerly the Portuguese Colónia do Sacramento) is a city in southwestern Uruguay, by the Río de la Plata, facing Buenos Aires, Argentina. It is the oldest town in Uruguay and capital of the departamento of Colonia. It has a population of 21,714 (2004 census).

It is renowned for its historic quarter, a World Heritage Site. Modern Colonia del Sacramento produces textiles and has a free trade zone, in addition to a polytechnic center and various government buildings.