Born in Florence as Giambattista Strozzi, he was rechristened by his mother with the name of his father Filippo Strozzi the Elder, who had died two years after his birth.
Filippo Strozzi began his career as treasurer at Ferrara in 1513, and soon became a prominent figure in Florence's politics and economics. Although in natural competition with the other main family of the city, the Medici, he managed to ally with them through his marriage when the Medici were living in exile. When the latter returned in Florence, Strozzi obtained important political and diplomatic positions. However, when Lorenzo was replaced by Leopoldo and Alessandro de' Medici, he and his son Piero started to be looked as enemies by the new lords. Rumours about alleged Piero's (who was indeed son of a Medici) claims about the lordship of Florence reached Pope Clement VII who menaced the Strozzis of punishments. When Clarice died, the strain became unbearable: therefore Filippo and Piero self-exiled to Rome, in order to escape a likely attack from the ruthless Alessandro.
In Filippo's house in Rome Catherine de' Medici, the future queen of France, and Lorenzino de' Medici were educated. It is likely that Filippo himself prompted the latter to his assassination of the tyrannic Alessandro (1537). In the same year the Strozzi assembled an army, including numerous other Florentine exiled, and marched against Florence from France. the Strozzi army was first halted at Sestino by troops hastily mustered by the new Medici lord, the future Cosimo I. The decisive battle occurred on August 1, 1537 at Montemurlo. Cosimo's army, supported by Spanish troops, was victorious. Filippo Strozzi was imprisoned, while his sons escaped to Venice and then to France.