Moneo is one of Spain's most prestigious architects whose works include the Los Angeles Cathedral and the Atocha railway station in Madrid.
The Prince of Asturias Foundation said Moneo's "work enriched urban space with a serene and meticulously tidy architecture."
The prize was announced Wednesday as Moneo turned 75. He already won the Pritzker Architecture Prize in 1996.
Eight Asturias prizes are awarded each year covering the arts, human rights, sciences and sports.
They include a (EURO)50,000 ($65,000) cash award and a sculpture by Joan Miro. They are presented by Spain's crown prince each autumn in Oviedo.