Della Rovere reaches France and strikes a bargain with its ruler to invade Italy and install him on the Papal throne in exchange for control of Naples; Rodrigo attempts to thwart the invasion through an alliance by marrying his youngest son Joffre to Princess Sancia of Naples (guest star Emmannuelle Chriqui), but Juan nearly sabotages the plan by seducing his prospective sister-in-law.

The invasion by King Charles of France and Della Rovere proceeds with victory seemingly inevitable as the French sack the city of Lucca and the Italian powers flee to their banner, with Lucrezia's husband Giovanni Sforza poised to join them in the name of Milan; inventor Leonardo Da Vinci (guest star John Lynch) shows his drawings and blueprints for war machinery to the invaders.

Abandoned by even his cardinals, Alexander meets King Charles with humility and saves his throne, even eliciting a confession from the conqueror he crowns as the new "King of France and Naples;" Della Rovere despairs as Charles abandons him; Lucrezia safely gives birth to a son in a convent as the Borgias secure an annulment of her marriage and plot revenge on their enemies.