Although its oratory is a more intriguing artistic expression because of the delightful putti by Giacomo Serpotta, the Church of St. Dominic is one of the city's most remarkable baroque structures, its elegant baroque facade often depicted on postcards. It was constructed in 1640 to the design of the architect Andrea Cirrincione. The facade, however, wasn't added until 1726. Many antique buildings on the square were demolished to give this church more breathing room.

The facade rises in a trio of carefully ordered tiers, graced with both Corinthian and Doric pillars along with square pilasters that form a sort of picture frame for a statue of St. Dominic. Unlike the lavishly decorated oratory, the church has a severe interior that only emphasizes the beauty of the architecture. Its chapels, on the other hand, are richly decorated, forming a pantheon of tombs and cenotaphs of some of the more noble Sicilians, including Francesco Crispi, the former prime minister of Italy. The tomb of the painter Pietro Novelli (1608-47) is in the north aisle.

Adjacent is the headquarters of the Sicilian Historical Society, with its own tiny Museo del Risorgimento (Resurgence Museum), containing mementos of Garibaldi. The fragmented 14th-century cloister was part of the first church erected on this site.