The ancient authors attribute the naming of the street or road as the Vicus Tuscus to two distinct events of Etruscan immigration and settlements in the history of ancient Rome, first around 750 BCE and second in 508 BCE. Tacitus, writing in the later first century or early second century CE, says the name arose from the Etruscans who had come to aid the Romans against Titus Tatius, a Sabine ruler who invaded Rome in around 750 BCE after Romans had abducted Sabine women, and later settled down in the neighborhood of the Roman forum. Livy, on the other hand, says the name came from the remnants of the Clusian army who settled in the area following the War between Clusium and Aricia in 508 BCE.

However, some traditions note that the settlement was composed of labourers and workers who were involved in Rome was to construct the Temple of Jupiter Optimus Maximus. Dionysius, in his The Roman antiquities, notes that the Roman senate provided Etruscans a place to build houses near the Vicus Tuscus.

Today, only the left (east) side of the extant Vicus Tuscus has been excavated and the right (west) side still remains unexcavated at large.

circa 750 BCE

The area of and aound the Vicus Tuscus was originally the site of residential complexes belonging to the wealthy families, during the Roman Kingdom and early Roman Republic periods. However, by the later Republican times, the Vicus Tuscus had became a hub of Roman commerce when a number of horrea (warehouses or storehouses) were built here. According to the historical sources there were many stores (horrea) on both sides of the Vicus Tuscus, which included grain, and other commodities as well as booksellers. According to Horace's Epistles, books were on sale, along the lenght of the street, in front of the statues of Etruscan god Vertumnus (god of seasons) and Janus Geminus (god of passages) in the Tuscan street and inside the Forum. The most influential merchants were expert dealers of incense and perfume (called turarii in Latin), giving rise to the street's second name - Vicus Turarius. Propertius recorded that these tradesmen made sacrificial offerings to Vertumnus, whose statue stood on Vicus Tuscus.

circa 50 BCE- 100 CE

Roman Empire
During antiquity the Vicus Tuscus, started at the juction with Via Sacre near the Basilica Julia and Temple of Castor and Pollux and ran south-west out of the Roman Forum passing in front of the Horrea Agrippiana, and the adjancet tabernae situated along the western footing of the Palatine Hill. After leaving the Forum area, it proceeded towards the Forum Boarium and Circus Maximus via the west side of the Palatine Hill and Velabrum.

During this period the ancient Vicus Tuscus was frequently used as an important path of mobility between the Roman Forum and the Forum Boarium and Circus Maximus. When Romans conducted a sacrificial rite to their gods, two white cows were led through Vicus Tuscus and Velabrum via the forum Boarium, to arrive at the Temple of Juno Regina on the Aventine Hill.

During the Ludi Romani (the Roman Games; a religious festival in ancient Rome held annually, starting in 366 BCE, from September 12 to September 14), the Vicus Tuscus was a route for processions. Statues of gods on carts, flotilla, or wagons were paraded through here from the Capitoline Hill to reach the Circus Maximus. Plautus notes (Curculio, IV 482) that around 193 BCE, this was the spot for male prostitution in Rome.

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Basilica Julia
The east end of the Basilica Julia was connected to the Vicus Tuscus, for a length of approx. 60 meters.

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Temple of Castor and Pollux
The Temple of Castor and Pollux, situated directly opposite the Basilica Julia, stood on the east flank of the Vicus Tuscus, where is branched off from the Via Sacra.

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Horrea Agrippiana
The Horrea Agrippiana (warehouses of Agrippa) were situated south of the Temple of Castor and Pollux on the eastern side of the road.

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Tabernae
A number, several, tabernae were located on either side of the Vicus Tuscus.

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Shrine of Vertumnus
The shrine of Vertumnus (or Vortumnus), who was the god of seasons, change and plant growth, as well as gardens and fruit trees. Most historical sources and modern day academics and historians place the shrine on the Vicus Tuscus behind the Temple of Castor and Pollux. The statue or shrine of Vertumnus, according to Plautus (a Roman playwright of the Old Latin period), writing in circa 160 BCE, was situated in the Velabrum, which constituted a large area between the Roman Forum and the Tiber River. The statue or shrine of Vertumnus is also known from a mention by Cicero (Verr. 2.I.59 [154]).

circa 15 CE

Temple of Augustus
Although the exact location of the Temple of Augustus is not known, the large structure north of the Horrea Agrippiana has been tentatively identified as the Augustan Temple. The Temple of Divus Augustus was a major temple originally built to commemorate the deified first Roman emperor, Augustus. It was built between the Palatine and Capitoline Hills, behind the Basilica Julia, on the site of the house that Augustus had inhabited before he entered public life in the mid-first century BCE. It is known from Roman coinage that the temple was originally built to an Ionic hexastyle design. However, its size, physical proportions and exact site are unknown. The temple's construction took place during the first century CE, having been vowed by the Roman Senate shortly after the death of the emperor in 14 CE.