San Giovanni in Croce borders the following municipalities: Casteldidone, Gussola, Martignana di Po, Piadena, Solarolo Rainerio.

The earliest records of the comune's origin are found in a deed dated 10 December 1022, in which Marquis Bonifacio of Tuscany is said to be indebted to the bishop of Cremona for some land in Palvareto, the oldest nucleus of San Giovanni, which was located around the old parish church.

In May 2014, after becoming its owner in 2005 and following a major restoration project, the municipality returned to public enjoyment the monumental and naturalistic complex of Villa Medici del Vascello, now a destination for significant cultural tourism attracted, in particular, by the figure of Cecilia Gallerani, the subject of the Lady with an Ermine portrayed by Leonardo da Vinci, who became Countess of San Giovanni in Croce in July 1492.

It was in honor of Cecilia Gallerani that the local municipal theater, which features an interesting Art Nouveau facade, was named in November 2002.

Between 1888 and 1928, the same locality was also served by the Ca' de Soresini-San Giovanni in Croce branch line of the Cremona-Casalmaggiore tramway, ultimately operated by the Tramvie Provinciali Cremonesi company