Construction of the cathedral of Santa Maria del Fiore began in 1296 under Arnolfo di Cambio and continued for more than a century before the cathedral's defining feature, Brunelleschi's dome, was begun in 1420. The dome was completed in 1436 and remains the largest brick dome ever built. At 42 meters internal diameter and 114 meters from the floor to the top of the lantern, it is the largest single architectural feature in Renaissance Florence and one of the most consequential single structures in the entire history of Western architecture.

Brunelleschi's solution to the dome problem, how to span 42 meters without external buttresses or internal centering, was engineering innovation on the scale of the Pantheon's concrete dome thirteen centuries earlier. His double-shell design, the herringbone brickwork that allowed the dome to be self-supporting during construction, and the catenary curve profile became foundational techniques of Renaissance and later European architecture. The dome was the structural argument by which Brunelleschi established Renaissance architecture as a discipline distinct from medieval building tradition.

The cathedral is the third-largest church in Europe by interior volume (after St Peter's Basilica in Rome and St Paul's Cathedral in London). The polychrome marble facade was added in the 1880s in the Gothic Revival style to a design by Emilio De Fabris, replacing an earlier unfinished facade. The cathedral, the Baptistery, and Giotto's Campanile together form the centerpiece of the Florentine UNESCO World Heritage Site and the architectural anchor of one of the most-visited European city centres.