The name originates from its role as vacation resort for the ancient Roman gens Genucia. In the fifth century, during the reign of Pope Sixtus III, the town of Genazzano contributed a large portion of its revenue for the Roman basilica of Santa Maria Maggiore. In the 11th century AD it was a fief of the Colonna family who, from their Baronal Palace (castle), controlled the road from Naples to Rome. In the late fiftenth century, it became fief of the Borgia Family.
The church of the Madonna del buon consiglio, built in appreciation for the town's contribution to Sana Maria Maggiore, and entrusted in 1356 to the Augustinian Order, holds the original fresco of Our Lady of Good Counsel (Latin: Mater boni consilii) a title given to the Blessed Virgin Mary, after the allegedly miraculous fresco. Measuring 40 by 45 centimetres (16 by 18 in), the image is executed on a thin layer of porcelain no thicker than an egg shell. Over the centuries, devotions to Our Lady of the Good Counsel grew among saints and Popes. More than any other pope, Leo XIII was deeply attached to this devotion. The small Scapular of Our Lady of Good Counsel (the White Scapular) was presented by the Hermits of St. Augustine to Pope Leo XIII, who, in December 1893, approved it and endowed it with indulgences. On 22 April 1903, that same Pope included the invocation "Mater boni consilii" in the Litany of Loreto.
At the southern end of the village, there is a Nymphaeum built at the dawn of the 16th century and attributed to Donato Bramante.