Jose Antonio Urrutikoetxea Bengoetxea, better known as Josu Ternera and who was once ETA's political chief, was detained “in the early hours of the morning today in Sallanches in the French Alps,” the ministry said.
ETA killed more than 800 people in more than four decades of violence for an independent Basque state.
Spanish authorities have been trying to track Ternera down since 2002, linking him to an attack on a police barracks in the northern city of Zaragoza in 1987 which left 11 people dead, including children.
Hugely influential within the group, Ternera, who is believed to be seriously ill, recorded the “final declaration” announcing the separatist group had completely dissolved in May 2018.
Before that, he had taken part in negotiations with Spain's Socialist government and was shunted aside in 2006 after the talks failed as more hardline elements took control.