BARCELONA—Hundreds of thousands of protesters converged in Barcelona for a general strike, paralyzing the city as violent clashes erupted and forcing the shutdown of its famed Sagrada Familia basilica amid renewed calls for Catalonia to secede from Spain.

The latest wave of unrest, triggered by the jail sentencing of separatist leaders earlier this week, has made the longstanding issue of Catalan independence once again central to Spain’s political debate as the country heads to parliamentary elections on Nov. 10.

Mass...