Rise to power
Cosimo was born in Florence on 12 June 1519, the son of the famous condottiere Ludovico de' Medici (known as Giovanni dalle Bande Nere) and his wife Maria Salviati. He was the grandson of Caterina Sforza, the Countess of Forlì and Lady of Imola. Cosimo came to power in 1537 at age 17, just after the 26-year-old Duke of Florence, Alessandro de' Medici, was assassinated. Cosimo was from a different branch of the Medici family, descended from Giovanni de' Medici il Popolano, the great-grandson of Giovanni di Bicci de' Medici, founder of the Medici Bank. It was necessary to search for a successor outside of the "senior" branch of the Medici family descended from Cosimo di Giovanni de' Medici, since the only male child of Alessandro, the last lineal descendant of the senior branch, was born out-of-wedlock and was only four years' old at the time of his father's death. Up to the time of his accession, Cosimo had lived only in Mugello (the ancestral homeland of the Medici family) and was almost unknown in Florence. However, many of the influential men in the city favoured him as the new duke. Several hoped to rule through him, thereby enriching themselves at the state's expense. However, as the Florentine literatus Benedetto Varchi famously put it, "The innkeeper's reckoning was different from the glutton's."  Cosimo proved strong-willed, astute and ambitious and soon rejected the clause he had signed that entrusted much of the power of the Florentine duchy to a Council of Forty-Eight.
When the Florentine exiles heard of the death of Alessandro, they marshalled their forces with support from France and from disgruntled neighbors of Florence. During this time, Cosimo had an illegitimate daughter, Bia (1537 – 1542), who was portrayed shortly before her premature death in a marvelous painting by Bronzino.
Toward the end of July 1537, the exiles marched into Tuscany under the leadership of Bernardo Salviati and Piero Strozzi. When Cosimo heard of their approach, he sent his best troops under Alessandro Vitelli to engage the enemy, which they did at Montemurlo. After defeating the exiles' army, Vitelli stormed the fortress, where Strozzi and a few of his companions had retreated to safety. It fell after only a few hours, and Cosimo celebrated his first victory. The prominent prisoners were subsequently beheaded on the Piazza della Signoria or in the Bargello. Filippo Strozzi's body was found with a bloody sword next to it and a note quoting Virgil, but many believe that his suicide was faked.
Rule of Tuscany
In 1537, Cosimo sent Bernardo Antonio de' Medici to Holy Roman Emperor Charles V to gain recognition for his position as head of the Florentine state. That recognition came in June 1537 in exchange for help against France in the course of the Italian Wars. With this move, Cosimo firmly restored the power of the Medici, who thereafter ruled Florence until the death of the last of the Medici ruler, Gian Gastone de' Medici, in 1737. The help granted to Charles V allowed him to free Tuscany from the Imperial garrisons and to increase as much as possible its independence from the overwhelming Spanish influence in Italy.
Cosimo next turned his attention to Siena. With the support of Charles V, he defeated the Sienese at the Battle of Marciano in 1554 and laid siege to their city. Despite the inhabitants' desperate resistance, the city fell on 17 April 1555 after a 15-month siege, its population diminished from forty thousand to eight thousand. In 1559, Montalcino, the last redoubt of Sienese independence, was annexed to Cosimo's territories. In 1569, Pope Pius V elevated him to the rank of Grand Duke of Tuscany.
In the last 10 years of his reign, struck by the death of two of his sons by malaria, Cosimo gave up active rule of the Florentine state to his son and successor Francesco I. He retreated to live in his villa, the Villa di Castello, outside Florence.