MADRID—Political leaders in Spain's wealthy Catalonia region have set a date for a referendum on declaring independence, but the Spanish prime minister flatly stated such a vote was unconstitutional and wouldn't be permitted.

The preparation for a secession vote in Catalonia, which has long chafed under what it calls economic and cultural dominance from Madrid, sets Spain's leading industrial region on a collision course with the central government. The stakes for both sides are enormous and the outcome hard to predict.

Catalan regional leader Artur Mas said Thursday that the region's major political parties had agreed on wording of a two-part question to be put on a ballot Nov. 9, 2014.

The first part is: "Do you want Catalonia to be a State?" The second part is: "Do you want Catalonia to be an independent State?"

Mr. Mas, who had pledged to hold a referendum after elections last year, said the question was "inclusive, and at the same time, clear and concrete." He added that there would be more details in coming days on how the vote would be conducted.