The San Ġwann suburb is mostly made up of relatively modern buildings. However, the few scattered archeological remains in the region suggest that San Gwann’s ancient history is woven into the national history of Malta.
The oldest human remains in the locality are the cart ruts close to Sant Andrija zone, probably pre dating the Punic Period, about to 2300-1000 BC.
These prehistoric cart ruts suggest that the region may have housed an agricultural community cultivating the then fertile valleys of Wied Għomor, Wied il-Ballut and Wied Għollieqa. These prehistoric inhabitants may have lived in nearby natural caves. In Wied Għomor, there are also a number of megalithic-type stone blocks that may have belonged to a Neolithic structure. This agricultural community continued with its activities throughout the subsequent centuries. Roman tombs and a covered cistern have been excavated from the region. However, the most renowned period archaeological remain is the "Roman Tower" of Ta’ Ċieda. This tower was one of eight defensive towers built throughout Malta around the 3rd century AD. During the Arab period the region was used as a cemetery.
The Arab links to the region can also be seen in the various Semitic names given to various localities as arrested by various medieval notarial documents. The old names given to the region – Tal-Għargħar, and L-Imsieraħ – are such examples. During the medieval period, the region was apparently inhabited by at least two communities living at Raħal Tigan and Raħal Ger between Tal-Għargħar and Naxxar.
The Għargħar [sive`Arar] region during the Medieval period also apparently housed the parochial church of St. Helena, abandoned during the 14th century, and situated possibly close to the Ta’ Ċieda Tower. The cave-chapel of San Leonardo is today known as the Chapel of the Annunciation [Lunziata Chapel].
The coming of the Order of St. John in 1530 and the aftermath of the 1565 Great Siege brought a degree of safety from recurrent Turkish raids which led to an increase in the population. Besides chapels, structures built during the time of the knights included Torri ta’ Lanzun (a protected farm-building [c.1713].
The Għargħar rise became an important outpost for the Maltese troops blockading the French forces within the capital in 1798-1800. The Ta’ Xindi Farmhouse was served as headquarters of Captain Vinċenzo Borg (Brared).
The area was little affected by the Second World War, though Torri Lanzun was damaged during enemy action. The locality featured in plans of the British Colonial Office in its overall defence scheme in the eventuality of a possible nuclear attack. The Colonial Office initiated the building of eight underground flour mills in Malta and Gozo. One such mill with a silo is located behind the San Ġwann State Primary School.
The 1950s also led to the construction of a convent by the Capuchin Friars and a new church that was completed in December 1959 which become the Parish Church in 1965. It adopted the name from the old chapel of San Ġwann tal-Għargħar.
The San Ġwann community increased significantly in the 1970s. In 2005 the population was registered at 12630 individuals. The Local Councils Act of 1993 identified San Gwann as a separate district with its own statutory local government authority. The first San Ġwann Council was elected on 16th April 1994.