She was the daughter of a wealthy Florentine banker, and her portrait—the only painting by Leonardo da Vinci in the Americas—was probably commissioned about the time of her marriage at age 16. Leonardo himself was only about six years older. The portrait is among his earliest experiments with the new medium of oil paint; some wrinkling of the surface shows he was still learning to control it. Still, the careful observation of nature and subtle three–dimensionality of Ginevra's face point unmistakably to the new naturalism with which Leonardo would transform Renaissance painting. Ginevra is modeled with gradually deepening veils of smoky shadow—not by line, not by abrupt transitions of color or light.

Other features of Ginevra's portrait reveal young Leonardo as an innovator. He placed her in an open setting at a time when women were still shown carefully sheltered within the walls of their family homes, with landscapes glimpsed only through open windows. The three–quarter pose, which shows her steady reserve, is among the first in Italian portraiture, for either sex.

At some time in the past, probably because of damage, the panel was cut down by a few inches along the bottom, removing Ginevra's hands. A drawing by Leonardo survives that suggests their appearance—lightly cradled at her waist and holding a small sprig, perhaps a pink, a flower commonly used in Renaissance portraits to symbolize devotion or virtue. Ginevra's face is framed by the spiky, evergreen leaves of a juniper bush, the once–brighter green turned brown with age. Juniper refers to her chastity, the greatest virtue of a Renaissance woman, and puns her name. The Italian for juniper is _ginepro_.

The vast majority of female portraits were commissioned on one of two occasions: betrothal or marriage. Wedding portraits tend to be made in pairs, with the woman on the right side. Since Ginevra faces right, this portrait is more likely to have commemorated her engagement. Her lack of obvious finery, however, is somewhat surprising. Jewels, luxurious brocades, and elaborate dresses were part of dowry exchanges and displayed a family’s wealth.