An early depiction of Lassie is found in British Writer Elizabeth Gaskell's 1859 short story "The Half-brothers". In the story, Lassie is described as a female collie with "intelligent, apprehensive eyes" who rescues two half-brothers who are lost and dying in the snow. When the younger brother can no longer carry on, elder brother Gregory, Lassie's master, ties a handkerchief around Lassie's neck and sends her home. Lassie arrives home, and leads the search party to the boys. When they arrive Gregory is dead, but his younger half-brother is saved. Thus, Gaskell apparently originated the character Lassie, and at the same time defined the "Lassie saves the day" storyline that is the essence of subsequent Lassie tales.

Half collie, Lassie was owned by the landlord of the Pilot Boat, a pub in the port of Lyme Regis. On New Year's Day in 1915 the Royal Navy battleship Formidable was torpedoed by a German submarine off Start Point in South Devon, with the loss of more than 500 men. In a storm that followed the accident, a life raft containing bodies was blown along the coast to Lyme Regis. In helping to deal with the crisis, the local pub in Lyme Regis, called the Pilot Boat, offered its cellar as a mortuary.

The fictional character of Lassie was created by English American author Eric Knight in Lassie Come-Home, first published as a short story in The Saturday Evening Post in 1938 and later as a full-length novel in 1940. Set in the Depression-era England, the novel depicts the lengthy journey a rough collie makes to be reunited with her young Yorkshire master after his family is forced to sell her for money.

Published in 1940, Knight's novel was filmed by MGM in 1943, as Lassie Come Home with a dog named Pal playing Lassie. Pal then appeared with the stage name "Lassie" in six other MGM feature films through 1951. Pal's owner and trainer Rudd Weatherwax then acquired the Lassie name and trademark from MGM and appeared with Pal (as "Lassie") at rodeos, fairs, and similar events across America in the early 1950s. In 1954, the long-running, Emmy winning television series Lassie debuted, and, over the next 19 years, a succession of Pal's descendants appeared on the series. The "Lassie" character has appeared in radio, television, film, toys, comic books, animated series, Juvenile novels, and other media. Pal's descendants continue to play Lassie today.

In 1943, the novel was adapted into a feature film, Lassie Come Home, by Metro-Goldwyn-Mayer (MGM) that starred Roddy McDowall and Elizabeth Taylor. The movie was a hit and enjoyed favorable critical response. MGM followed this with several additional films, including a sequel entitled Son of Lassie (1945), starring Peter Lawford and June Lockhart, and Courage of Lassie with Elizabeth Taylor. A radio series, Lassie Radio Show, was also created, airing until 1949.

Between 1954–1973, the television series, Lassie was broadcast, with Lassie initially residing on a farm with a young male master. In the eleventh season, it changed to U.S. Forest Service rangers as her companions, then the collie was on her own for a season before ending the series with Lassie residing at a ranch for orphaned children. The long-running series was the recipient of two Emmy Awards before it was canceled in 1973. A second series followed in the 1980s. In 1997, Canadian production company Cinar Inc. produced a new Lassie television series for the Animal Planet network in the U.S. and YTV in Canada. It ran until 1999.

In 2005, a remake of the original Lassie Come Home movie was produced in the United Kingdom. Starring Peter O'Toole and Samantha Morton, Lassie was released in 2006.

An animated TV series was made based on the dog. It was called "The New Adventures of Lassie". In this animated TV series Lassie was a dog that was owned by the Parker family in a national park. The animated TV series is mainly a traditionally-animated (2D hand-drawn animated) TV series with some CGI animation (vehicles) in it. The TV series was shown on TVOntario in Ontario, Canada from 2013 to 2016.

Lassie continues to make personal appearances as well as marketing a line of pet food and a current pet care TV show, Lassie's Pet Vet on PBS stations in the United States. Lassie is one of only three animals (and one of very few fictional characters, such as Mickey Mouse, Kermit the Frog, and Bugs Bunny) to be awarded a star on the Hollywood Walk of Fame—the others being silent-film stars Rin Tin Tin and Strongheart. In 2005, the show Business journal Variety named Lassie one of the "100 Icons of the Century"—the only animal star on the list.