Although these machines were not widely known, the vehicle performed well in its role. Though it was technically similar to the StuG III, it had a totally different role, serving as divisional artillery instead of a pure assault gun. The organic structure consisted of two artillery groups for every armoured division, with two batteries each (four 75/18 each and a command vehicle). The total was of 18 75 mm L/18 (included two in reserve) and 9 command vehicles, which were characterized by additional radio equipment and a 13 mm machine gun mounted instead of the main gun. The number originally ordered, 60 total, was enough for the three armoured divisions.
The Semovente 75/18s were deployed in the North African campaign and during the Allied invasion of Sicily, alongside M tank units to provide additional firepower. Despite the fact that they were not designed to fight other tanks, their 75 mm howitzer proved ideal (thanks to its low muzzle velocity) for firing HEAT shells; its 5.2 kg HEAT shell ("Effetto Pronto" in Italian) could pierce 70 mm of armour at 500 meters, thus being able to defeat tanks such as the US built M3 Grant and M4 Sherman used by the British Army. As such, these machines were responsible for many of the successes by the Italian armoured troops during 1942–43, when the medium tanks (all armed with a 47 mm gun) could no longer be competitive.
Despite its limitations (namely its cramped interior and the insufficiently powerful engine in the M40 and M41 variants), the Semovente da 75/18 proved successful both in the direct support role and in anti-tank fighting; its main advantages, other than their sheer firepower, was in its thicker armour (relative to the medium tanks) and lower silhouette that made it more difficult to hit. However, as it was never deployed en masse, the scarce number of Semoventi on the field (no more than 30 at the time of the Second Battle of El Alamein) wasn't enough to turn the tide in Italy's favour.
In 1942, more vehicles were built: 162, all with the M41 hull, recognizable by the all-length fenders; in 1943, production shifted to the M42 variant, with the M15/42 tank chassis and engine. It was also decided to address the shortcomings of the M14/41 tank by bolstering each unit with some Semoventi, even outside the three armoured divisions fielded, even though very few Italian divisions actually received any.
The necessity for a longer and more powerful gun led to the development of the 75/34, 75/46 and 105/25 self-propelled guns.
After the Italian surrender in 1943, some 131 Semovente 75/18 were seized by the Germans and the production of another 55 was authorized. They were issued to six infantry divisions, two panzer divisions, three Panzergrenadier divisions, 22 SS Volunteer Cavalry Division Maria Theresa and one Gebirgsdivision intended for service in Italy and the Balkans.