The Guadiana River (ˌɡwɑːdiˈɑːnə, also USɡwɑːdˈjɑːnə, ɡwaˈðjana, ɡwɐðiˈɐnɐ), is an international river defining a long stretch of the Portugal-Spain border, separating Extremadura and Andalusia (Spain) from Alentejo and Algarve (Portugal). The river's basin extends from the eastern portion of Extremadura to the southern provinces of the Algarve; the river and its tributaries flow from east to west, then south through Portugal to the border towns of Vila Real de Santo António (Portugal) and Ayamonte (Spain), where it flows into the Gulf of Cádiz. With a course that covers a distance of , it is the fourth-longest in the Iberian peninsula, and its hydrological basin extends over an area of approximately (the majority of which lies within Spain).
The Romans referred to the river as the Flumen Anas, the "River of Ducks". During the Moorish occupation and settlement, the name was extended and referred to as Wadi Ana (wādī being the Arab term for "river"), later passed on to Portuguese and Spanish settlers as the Ouadiana, and later just Odiana. Since the 16th century, the name slowly evolved to take on the form Guadiana, a cognitive variation that developed from many Moorish-Arab river place-names using the prefix guad- (such as the hydronyms Guadalquivir, Guadalete, or Guadarrama).
The Guadiana flows east to west through Spain and south through Portugal, then forms the Spanish-Portuguese border; it flows into the Gulf of Cádiz, part of the Atlantic Ocean, between Vila Real de Santo António (Portugal) and Ayamonte (Spain). It is long, of which are within Spanish territory, within Portugal, while are shared between the two nations. About 82 percent, , of its basin is in Spain, while about 17 percent, is in Portugal.
The exact source of the river in Castilla-La Mancha is disputed, but it is generally believed to spring in the Ojos del Guadiana, Villarrubia de los Ojos municipal term, Ciudad Real Province, Castile–La Mancha, about in elevation.