It was a battle between the Imperial troops and its allies Duchy of Florence and France and its allies the Republic of Sienna on the countryside of Marciano della Chiana, near Arezzo, Tuscany, on August 2, 1554, during the Italian War of 1551. The battle marked the defeat of the Republic of Siena in its war against the Duchy of Florence, and resulted in Siena losing its independence and being absorbed into the Grand Duchy of Tuscany.

In 1554, Cosimo I de' Medici, with the support of Emperor Charles V, launched a grand campaign to conquer Florence's last remaining rival in Tuscany, the Republic of Siena. His army was under the command of Gian Giacomo Medici, Marquess of Marignano, best known as "Medeghino" ("Small Medici"). The Florentine-Imperial troops were divided into three corps: Federico Barbolani di Montauto, with 800 men, landed in southern Tuscany to conquer the area of Grosseto; Rodolfo Baglioni, with 3,000 men, invaded the Val di Chiana to conquer Chiusi, Pienza and Montalcino; and the main corps under Medeghino himself, consisting of 4,500 infantry, 20 cannons, and 1,200 sappers, was deployed at Poggibonsi for the main attack against Siena.

The Senese entrusted the defence to Piero Strozzi, a fierce rival of the Medici family and a general in French service. French troops, as well as some Florentine exiled by the Medici, took part to the war under the Sienese aegis.After some days of inactivity, Medeghino raised the siege of Siena and moved to meet Strozzi.

After some initial skirmishes, the two large armies clashed when Strozzi, short of food, decided to retire towards Lucignano in the night of August 1. In the morning of the following day, it was clear that his manoeuver had not been successful, and he was forced to lay battle against the Florentine-Imperial troops that were stalking and harassing his moving troops.

The Senese had: c. 1,000 French-Senese horse on the right wing; then followed, on the centre, 3,000 Landsknechts, with 3,000 Grisons infantry behind them and other 3,000 French infantry on their left; the left wing was formed by 5,000 Italian infantry under Paolo Orsini. Strozzi's army occupied the slight slope of a hill that descended towards the Scannagallo creek. Il Medeghino deployed 1,200 light cavalry on his left wing, backed by 300 Uomini-d'Arme (heavy cavalry) under Marcantonio Colonna. The centre infantry corps was composed by 2,000 Spanish veterans and other Corsican recruits and 4,000 German Landsknechts under Niccolò Madruzzo. The right wing was formed by 4,000 Tuscan, 2,000 Spanish and 3,000 Roman poorly trained infantry, in three rows, with the few artillery available behind. The reserve included 200 Spanish soldiers, veterans of the Ottoman–Habsburg wars, and a company of horse arquebusiers from Naples.

The battle began with the attack of the Medeghino's cavalry wing, whose impetus easily routed its French-Senese counterpart, which fled towards Foiano. It has been reported that the French commanders of that unit, Valleron and Fourquevaux, had been bribed by the Medeghino with 12 tin flasks filled with golden coins.

To counter this first setback, Strozzi decided to launch down from the hill the German infantry of his center. A chaotic melee ensued, but soon the momentum of the Senese attack began to wane under the fire of the Imperial artillery, which also disorganized the Swiss attempting to relieve the first line. When Il Medeghino ordered also to his men to launch themselves against the enemy, the German and Swiss began to panic. This turned into a complete route when Colonna's heavy cavalry, who had pursued for a while the French-Senese cavalry, attacked from behind the Germans fighting across the Scannagallo. The French infantry on the right wing maintained its battle order, and, surrounded on every side, defended desperately until the end.

Strozzi himself was wounded three times and was carried away by his guards. His lieutenant Clemente della Cervara died shortly afterwards the battle for the wounds received.

The battle lasted for only two hours, from 11 AM to 1 PM. The Senese army suffered 4,000 dead, 4,000 wounded or prisoners. Strozzi escaped the capture.

Il Medeghino easily subdued the neighbouring castles in the days following the battle, and was subsequently able to lay a tighter siege to Siena. Cruel measures were adopted to prevent the peasants taking supplies into the city. In March 1555 he destroyed a corps of 1,300 mercenaries trying to escape to collect food.

Unable to receive substantial supplies and reinforces from the French, the city surrendered on April 17, 1555 while the remaining Senese forces withdrew to Montalcino.

The Republic of Siena finally disappeared in 1559 and was thenceforth incorporated into the Grand Duchy of Tuscany. The Grand Duke ordered that a large fortress be constructed as a precaution against the risk of further rebellion by the Sienese, and this has presided over the city, from its south-eastern Florentine side, since its completion in 1563.