From the city of Puerto Bahia Negra, Paraguay, the river forms the border between Paraguay and Brazil, flowing almost due south before the confluence with the Apa River.
Some 400km after flowing through the middle of Paraguay, at the confluence with the Pilcomayo River and passing the Paraguayan capital city, Asunción, the river forms the border with Argentina, flowing generally south-southwesterly for another 275km before it reaches its end, joining with the Paraná River.