[1][2] During World War II, the regiment was assigned to the 44th Infantry Division "Cremona", with which it fought in the Italian invasion of France.

After the announcement of the Armistice of Cassibile on 8 September 1943, the "Cremona" division fought German units retreating through Corsica.

The regiment's anniversary falls on 1 November 1916, the day during the Ninth Battle of the Isonzo the Brigade "Cremona" attacked Austro-Hungarian positions at Jamiano on the Karst plateau.

Initially the King's intention was to use the army against his own citizens, if they would rise against the Savoyard dynasty, but on 18 March 1848, the people of Milan, which was the capital of the Habsburg ruled Kingdom of Lombardy–Venetia, rose up and in five days of fighting drove the Austrian forces out of the city.

On 23 March 1848, King Charles Albert declared war on the Austrian Empire in the hope that he could use the rebellions in Lombardy–Venetia to expand his own kingdom.

By 19h in the evening of 4 August 1848, the Sardinian troops had retreated within the walls of Milan, where one hour later King Charles Albert held a war council, which decided to abandon the city due to a lack of munitions and food.

Three days later, on 9 August, the Austrian General Heinrich von Heß and the Sardinian General Carlo Canera di Salasco signed an armistice, which stated that Charles Albert's troops would withdraw from the whole of the Kingdom of Lombardy–Venetia, and the Duchy of Parma and Piacenza and Duchy of Modena and Reggio, whose rulers would be restored to their thrones.

Charles Albert massed his army near Novara, while the Lombard Division under General Ramorino was sent to guard the Ticino river crossings at Pavia.

At noon on the same day the whole Austrian Army crossed the Ticino river at Pavia and, even though the 21st Infantry Regiment led Major Luciano Manara resisted for six hours, the Austrians fixed the 21st Infantry Regiment in place with a screening forces, while the main body of the army marched North towards Mortara and Vigevano.

[1] Ultimately the 21st Infantry Regiment was forced to retreat across the Po river, where it joined with the rest of the Lombard Division, which played no role in the remaining events of the war.

On 22-23 March 1849, Field Marshal Radetzky decisively defeated the Sardinians in the Battle of Novara and on the evening of the same day King Charles Albert abdicated in favour of his son Victor Emmanuel.

On 24 March, the new king met with Radetzky at Vignale and agreed to an armistice, which ended the short Second Campaign of the First Italian War of Independence.

On 5 May 1860, Giuseppe Garibaldi's Expedition of the Thousand set off, with the support of the Sardinian government, from Genoa and landed on 11 May in Marsala in Sicily.

In 1887-88 the 21st Infantry Regiment's 1st Company deployed to Massawa for the Italo-Ethiopian War of 1887–1889, which led to the establishment of the Italian colony of Eritrea.

At the time the 21st Infantry Regiment consisted of three battalions, each of which fielded four fusilier companies and one machine gun section.

This time the brigade attacked towards San Martino del Carso on the Karst plateau and suffered more than 1,100 casualties for limited gains.

In August 1916, during the Sixth Battle of the Isonzo, the brigade initially remained inactive at Vermegliano, but after Italian forces conquered the Austro-Hungarian summit positions on Monte San Michele on 10 August, the Austro-Hungarians had to fall back and the Brigade "Cremona" pursued them on the Karst plateau to the hills overlooking the Doberdò lake: the 21st Infantry Regiment towards Črni hrib hill and the 22nd Infantry Regiment towards Debeli hill.

On 31 October 1916, the Ninth Battle of the Isonzo began and on 1 November the Brigade "Cremaon" attacked from Doberdò lake towards Jamiano.

The 21st Infantry Regiment, which formed the Italian rearguard, blocked the pursuing enemy from crossing the Isonzo at Ložice.

After arriving in Carpeneto, the brigade was ordered to march to Campoformido and establish a blocking line North of it between Colloredo di Prato and Faugnacco.

On 1 November 1917, the remnants established a loose defense line on the Western bank of the Tagliamento river Southeast of Valvasone.

[1][4][5] For its conduct on the Karst plateau in August, September and November 1916, and for the bravery of its II Battalion on Monte Pertica on 25-27 October 1918, the 21st Infantry Regiment was awarded a Silver Medal of Military Valor, while the 22nd Infantry Regiment was awarded a Silver Medal of Military Valor for its conduct on the Karst plateau in August, September and November 1916, and for its bravery on Monte Asolone on 14 January 1918.

In 1935-36, the 21st Infantry Regiment "Cremona" provided two officers and 22 troops to units deployed to East Africa for the Second Italo-Ethiopian War.

On 8 November 1942, Allied forces landed in French North Africa and Germany and Italy reacted by occupying Vichy France.

The two German units moved along Corsica's Eastern coast towards the harbor of Bastia in the island's North, with the two Italian divisions attempting to block their escape.

[1][13][15][21] On 12 January 1945, the Combat Group "Cremona" entered the frontline between the railroad from Alfonsine to Ravenna and the Adriatic Sea.

On 2-3 March 1945, the 22nd Infantry Regiment "Cremona" eliminated a dangerous German salient at Torre Primaro on the lower Reno river.

On 6 April 1945, the allied 1945 spring offensive began and the combat group crossed the Senio river and liberated Alfonsine.

Next the combat group crossed the Santerno river and advanced North, liberating Adria, Chioggia, Mestre, and Venice.

In November 1968 the regiment was deployed in the Province of Vercelli to help rescue efforts after heavy floods had devastated the area.