Verrazzano left a detailed account of his voyages to North America, but little is known about his personal life. After 1506, he settled in the port of Dieppe in France, where he began his career as a navigator. He embarked for the American coast, probably in 1508 in the company of captain Thomas Aubert, on a ship called La Pensée, equipped by ship owner Jean Ango. He explored the region of Newfoundland, possibly during a fishing trip, and possibly the St. Lawrence river in Canada; on other occasions, he made numerous voyages to the eastern Mediterranean.

Despite his discoveries, Verrazzano's reputation did not proliferate as much as other explorers of that era; for Example, Verrazzano gave the European name Francesca to the new land which he had seen, in accordance with the practices of the time, after the French king in whose name he sailed. This and other names have not survived, which he bestowed on features that he discovered. He had the bad luck of making major discoveries within the same three-year period (1519 to 1521) when the dramatic Conquest of Mexico and Ferdinand Magellan's circumnavigation of the world occurred; Magellan himself did not complete the voyage, yet it brought him undying fame.

In September 1522, the surviving members of Ferdinand Magellan's crew returned to Spain, having circumnavigated the globe. Competition in trade was becoming urgent, especially with Portugal. King Francis I of France was impelled by French merchants and financiers from Lyon and Rouen who were seeking new trade routes, so he asked Verrazzano in 1523 to make plans to explore (on France's behalf) an area between Florida and Terranova, the "New Found Land", with the goal of finding a sea route to the Pacific Ocean. Within months, four ships set sail due west for the Grand Banks of Newfoundland, but a violent storm and rough seas caused the loss of two ships. The remaining two damaged ships, La Dauphine and La Normande, were forced to return to Brittany.

The monument further states on its east face, "A native of Val Di Greve in the Tuscany region of Italy, he studied navigation as a young man and became a master mariner. He was engaged by the King of France to lead a voyage to North America in 1524. The purpose of Verrazzano's journey was to learn more about the continent. Traveling in a small ship known as the Dauphine, he explored coastal areas from the present-day State of North Carolina to Canada, observing the natural abundance of the land and the vibrant culture of its native peoples. His voyage is the earliest documented European exploration of this part of the Atlantic Coast. This monument rests upon stone from Castello di Verrazzano, the explorer's ancestral home."

The consensus amongst scholars is that Giovanni da Verrazzano was born in Val di Greve, south of Florence, then the capital and main city of the Republic of Florence, the son of Piero Andrea di Bernardo da Verrazzano and Fiammetta Cappelli. It is generally claimed that he was born in the Castello di Verrazzano (it), hence its birth indicator (similar to Leonardo da Vinci). Some alternative theories have been elaborated; for Example, certain French scholarship assumes that Verrazzano was born in Lyon, France, the son of Alessandro di Bartolommeo da Verrazano and Giovanna Guadagni. "Whatever the case," writes Ronald S. Love, "Verrazzano always considered himself to be Florentine," and he was considered a Florentine by his contemporaries as well. He signed documents employing a Latin version of his name—"Janus Verrazanus"—and he called himself "Jehan de Verrazane" in his will dated 11 May 1526 in Rouen, France (preserved at the Archives départementales de la Seine-Maritime).

Verrazzano arranged a second voyage, with financial support from Jean Ango and Philippe de Chabot, which departed from Dieppe with four ships early in 1527. One ship was separated from the others in a gale near the Cape Verde Islands, but Verrazzano reached the coast of Brazil with two ships and harvested a cargo of brazilwood before returning to Dieppe in September. The third ship returned later, also with a cargo of brazilwood.

There are conflicting accounts of Verrazzano's demise. In one version, in 1528, during his third voyage to North America and after exploring Florida, the Bahamas, and the Lesser Antilles, Verrazzano anchored out to sea and rowed ashore, probably on the island of Guadeloupe. He was killed and eaten by the native Carib inhabitants. The fleet of two or three ships was anchored out of gunshot range, and no one could respond in time. Other sources suggest that Verrazzano was executed for piracy by the Spanish, at Puerto del Pico, Spain.

He stayed there for two weeks and then moved northwards. He discovered Cape Cod Bay, his claim proved by a map of 1529 which clearly outlined Cape Cod.

Verrazzano's reputation was particularly obscure in New York City, where the 1609 voyage of Henry Hudson came to be regarded as the de facto start of European exploration of New York, since he sailed for the Dutch, not the French. It was only with great effort in the 1950s and 1960s that Verrazzano's name and reputation were re-established as the European discoverer of the harbor, during an effort to name the newly built Narrows bridge after him.

In 1909, during the Hudson-Fulton Celebration, a bronze statue by Ettore Ximenes was installed in Battery Park in Manhattan.

A vessel of the Italian navy, a destroyer of the Navigatori class, was named after Verrazzano. She was launched in 1930 and sunk by a British submarine in 1942.

There are numerous commemorations of the Explorer on Staten Island, where the Verrazano-Narrows Bridge, over the opening of New York Harbor, is perhaps the best known. A Staten Island Ferry boat that served New York from the 1950s to the 1990s was also named for Verrazzano (the ferry was named the "Verrazzano", while the bridge is named "Verrazano", reflecting the confusion over the spelling of his name). A Little League team on Staten Island is also named for him.

In the 19th and early 20th centuries, there was a great debate in the United States about the authenticity of the letters that he wrote to Francis I describing the geography, flora, fauna, and native population of the east coast of North America. Others thought that it was true, and it is almost universally accepted as authentic today, particularly after the discovery of the letter signed by Francis I which referred to Verrazzano's letter.