A Porta Vercellina was part of the Roman walls of Milan; it was located in what is now Via San Giovanni sul Muro, at the corner of Via Meravigli.

In the 12th century, after Frederick I Barbarossa conquered and ravaged Milan, a new fortified walls system was built, enclosing a larger area, and Porta Vercellina was thus moved west, farther from the centre, to what is now Via Carducci, between the Basilica of Sant'Ambrogio and the Sforza Castle.

In the 16th century, during Spanish rule, the walls of Milan were again enlarged, and the gate moved again west, to what is now the corner between Via Toti and Corso Vercelli.

In 1873, when the boundaries of Milan were enlarged and the surrounding Comune dei Corpi Santi was annexed to the city, the tollgate at Porta Vercellina lost its purpose, and in 1885 the gate was finally demolished.

The most important building in the district is the church of Santa Maria delle Grazie, one of Milan's prominent landmarks as well as UNESCO World Heritage Site, which is known both for its architecture and for housing Leonardo da Vinci's The Last Supper mural.