Samantha (or the alternatively Samanta) is primarily used as a feminine given name. It was recorded in England in 1633 in Newton Regis, Warwickshire. It was also recorded in the 18th century in New England, but its etymology is uncertain. Speculation (without evidence) has suggested an origin from the masculine given name Samuel and anthos, the Greek word for "flower". One theory is that it was a feminine form of Samuel to which the already existing feminine name Anthea was added.

"Samantha" remained a rare name until the 1873 publication of the first novel in a series by Marietta Holley, featuring the adventures of a lady named "Samantha", wife of Josiah Allen. The series led to the rise in the name's popularity, ranking among the top 1,000 names for girls in the United States from 1880, the earliest year for which records are available, to 1902.

The name was out of fashion in the United States for the majority of the first half of the 20th century but reappeared among the top 1,000 names for girls in 1958, when it ranked in 998th position, and in 1959, when it ranked in 993rd place. It fell off the top 1,000 list again until 1964, when it reappeared in 472nd place and leapt another 293 places to 179th place in 1965, coinciding with the 1964 debut of the television show, Bewitched, featuring as a lead character a young witch named "Samantha Stephens".

The name has remained consistently popular in the United States since the 1960s. It has ranked among the top 200 names for girls since 1965 and among the top 100 names for girls since 1976. It was among the ten most popular names for American girls born between 1988 and 2006 and was among the top 100 names for American girls until 2020. It was the 105th most popular name for American girls born in 2021. It has also been well-used in other countries in English-speaking countries and in Mexico.

In Sri Lanka, Samantha is used as a masculine given name, being one of the forms of the name of the god Saman. This usage has no known connection with the feminine version.