From the Greek name Ἄλεξις (Alexis) meaning "helper" or "defender", derived from Greek ἀλέξω (alexo) meaning "to defend, to help". This was the name of a 3rd-century BC Greek comic poet, and also of several saints. It is used somewhat interchangeably with the related name Ἀλέξιος or Alexius, borne by five Byzantine emperors.

In the English-speaking world this name is more commonly given to girls. This is due to the American actress Alexis Smith (1921-1993), who began appearing in movies in the early 1940s. It got a boost in popularity in the 1980s from a character on the soap opera Dynasty.