The building was the creation of the emperor Hadrian and construction began in 121. It was officially inaugurated by Hadrian in 135, and finished in 141 under Antoninus Pius. Damaged by fire in 307, it was restored with alterations by the emperor Maxentius.

As an additional clever subtlety by Hadrian, Venus also represented love (Amor in Latin), and "AMOR" is "ROMA" spelled backwards. Thus, placing the two divinities of Venus and Rome back-to-back in a single temple created a further symmetry with the back-to-back symmetry of their names.

The temple was erected on the remains of earlier structures of Domus Transitoria and Domus Aurea, two mansions commissioned by the disgraced Emperor Nero. Buried intact beneath the temple is an elaborate domed rotunda from the Domus Transitoria, with marble-lined pools and paving in multicoloured opus sectile.

Unimpressed by Hadrian's architectural design for the temple, his most brilliant architect, Apollodorus, is said to have made a scornful remark on the size of the seated statues within the cellae, saying that they would surely hurt their heads if they tried to stand up from their thrones. Apollodorus was banished and executed not long after this. According to the ancient historian Ammianus Marcellinus, the temple was among the great buildings of Rome which astonished the Emperor Constantius II on his visit to the city in 357 CE.

The temple-sanctuary was closed during the persecution of pagans in the late Roman Empire. Restoration was performed under the short-lived usurper Eugenius (392–394 CE), a Christian sympathetic to pagan worship. However, as with many of Rome's majestic ancient buildings, the temple was later targeted for its rich materials. In 630 CE, with the consent of the Emperor Heraclius, Pope Honorius I removed the gilt-bronze tiles from the roof of the temple for the adornment of Saint Peter's Basilica.

A severe earthquake at the beginning of the 9th century CE is believed to have destroyed the temple. Around 850 CE Pope Leo IV ordered the building of a new church, Santa Maria Nova, on the ruins of the temple. After a major rebuilding in 1612 CE, this church was renamed Santa Francesca Romana, incorporating Roma's cella as the belltower. A somewhat fanciful veduta engraving by Giovanni Battista Mercati depicts the site in 1629 CE. The vast quantity of marble that once adorned the temple has all but disappeared due to its use as a raw material for building projects from the Middle Ages onwards. The Italian archaeologist Rodolfo Amedeo Lanciani makes reference to his discovery of a lime kiln in close proximity to the temple in his work "The Destruction of Ancient Rome".

Plan
The twin-temple was set on a platform measuring 145 metres (476 feet) x 100 metres (330 feet). The peripteral temple itself measured 110 metres (360 feet) x 53 metres (174 feet) and 31 metres (102 feet) high (counting the statues) and consisted of two main chambers (cellae), each housing a cult statue of a god—Venus, the goddess of love, and Roma, the patron goddess of Rome, both figures seated on a throne. The cellae were arranged symmetrically back-to-back. Roma's cella faced west, looking out over the Forum Romanum, and Venus' cella faced east, looking out over the Colosseum.

A row of four columns (tetrastyle) lined the entrance to each cella, and the temple was bordered by colonnaded entrances ending in staircases that led down to the Colosseum. The west and east sides of the temple (the short sides) had ten white marble columns (decastyle) while the south and north sides featured twenty columns (inspect). All of these columns measured 1.8 metres (5 ft 11 inch) in width, making the temple very imposing.

Due to the rebuilding by emperor Maxentius, a coffered vaulted ceiling replaced the original wooden roof and the walls were doubled in thickness to take the increased load. The walls were inset with niches with small statues between small red porphyry columns standing above the floor on a plinth, all fronted by a colonnade in red porphyry (now only visible in the "Roma's Cella" incorporated in to the Santa Francesca).

Cella of Venus
Within Venus' cella which faced east towards the Colosseum was another altar where newly wed couples could make sacrifices. Directly adjacent to this altar stood gigantic silver statues of Marcus Aurelius and Faustina the Younger.

Cella of Roma
Most of the west side remains of the temple of Venus and Roma, which consisted of the Cella dedicated to the Roma, are now incorporated in the church of Santa Francesca Romana. The cella itself forms the east courtyard of the church complex. Two passages on the flanks of the central apse connect the cella of Roma to the cella of Venus.