Antonio Ledezma, 62, "asked for political asylum in Spain after three years in prison and under house arrest in his country," government spokesman Inigo Mendez de Vigo told reporters.
"He is a reference in the Venezuelan people's struggle to regain freedom and democratic normality," he added.
A lawyer by profession, Ledezma was arrested and jailed in February 2015 over allegations he was plotting to overthrow the president, and had been under house arrest since August.
He escaped to Colombia last week and then made his way to Spain.
Ledezma has said he fled Caracas because Venezuelan military and intelligence officials had informed him of a "government plan" against him, though he provided no details.
Oil-rich but cash-poor Venezuela is facing a deepening political and economic crisis as Maduro has moved to marginalise opposition forces, which control the country's legislature, and stifle independent media.