The sculpture stands on a square base which has bronze relief panels depicting the story of Perseus and Andromeda, similar to a predella on an altarpiece.

When the piece was revealed to the public on 27 April 1554, Michelangelo's David, Bandinelli's Hercules and Cacus, and Donatello's Judith and Holofernes were already installed in the piazza.

Perseus stands naked except for a sash and winged sandals, triumphant on top of the body of Medusa with her head, crowned with writhing snakes, in his raised hand.

[2] Cellini's use of bronze in Perseus and the head of Medusa, and the motifs he used to respond to the previous sculpture in the piazza, were highly innovative.

[8] The politics of the Medici and Florence dominate the Piazza della Signoria, specifically making reference to the first three Florentine dukes.

Cellini made the conscious decision to work in this medium because by pouring molten metal into his cast, he was vivifying the sculpture with life-giving blood.

[15] Cellini was competing against monumental works of marble sculpture like Michelangelo's David and wanted to make a statement for himself and his patron, Cosimo I. Michael Cole specifically draws attention to the process of casting the Perseus.

A bronze cast of the sculpture was made in the early 19th Century and installed at Trentham Gardens, Staffordshire, England around 1840, where it is now a Grade II* listed structure.