Columbus led an expedition supported by the Catholic monarchs of Spain that sought to establish a new route to Asia, but instead he reached the Caribbean.
His arrival there marked the beginning of a period of European contact with the Americas that led to conquest and settlement – and the death of many millions of natives from disease and warfare.
Countries have argued over the explorer’s origins for years, with many claiming him as their own.
25 conflicting theories about his birthplace have been evaluated, including Poland, Great Britain, Greece, Portugal, Hungary and Scandinavia.
These new findings are based on more than two decades of research.
The investigation began in 2003, when José Antonio Llorente, a professor of forensic medicine at the University of Granada, and historian Marcial Castro exhumed what were believed to be the remains of Columbus from Seville Cathedral.
Columbus died in the Spanish city of Valladolid in 1506, but wished to be buried on the island of Hispaniola in the Caribbean Sea. His remains were brought there in 1542, but centuries later were moved to Cuba before finally being buried in Seville.
Researchers also took DNA samples from the tomb, as well as the bones of Columbus’ son, Hernando, and brother, Diego.
Since then, scientists have compared this genetic information with that of historical figures and relatives of the researcher to try to solve the mystery.
The previously widely accepted theory was that Columbus was born in Genoa in 1451 to a family of wool weavers.
But now they believe he lived in Spain – probably Valencia – and was Jewish. They believe he hid his parentage to avoid persecution.
About 300,000 practicing Jews lived in Spain before they, along with Muslims, were ordered to either convert to Catholicism or leave the country in 1492, the year Columbus landed in America.
Announcing the results of the research in the television documentary Columbus’s DNA: Its True Origins, Professor Llorente said they were “almost absolutely reliable”.
The programme, which aired on Spain’s national broadcaster RTVE on Saturday night, coincided with Spain’s National Day.
The day marks the explorer’s arrival in America.