When the puppies were weaned, he gave the mother to an officer and three of the litter to other Soldiers, but he kept a male and a female. He felt that these two dogs were symbols of his good luck. He called them Rin Tin Tin and Nanette after a pair of good luck charms called Rin Tin Tin and Nénette that French children often gave to the American Soldiers. Duncan sensed that Nanette was the smarter of the two puppies. (The Soldiers were usually told that Rin Tin Tin and Nénette were lucky lovers which had survived a bombing attack, but the original dolls had been designed by Francisque Poulbot before the war in late 1913 to look like Paris street urchins. Contrary to popular usage, Poulbot said that Rin Tin Tin was the girl doll.)

Following advances made by American forces during the Battle of Saint-Mihiel, Corporal Lee Duncan, an aerial gunner of the U.S. Army Air Service, was sent forward on September 15, 1918, to the small French village of Flirey to see if it would make a suitable flying field for his unit, the 135th Aero Squadron. The area had been subject to bombs and artillery, and Duncan found a severely damaged kennel which had once supplied the Imperial German Army with German Shepherd dogs. The only dogs left alive in the kennel were a starving mother with a litter of five nursing puppies, their eyes still shut because they were less than a week old. Duncan rescued the dogs and brought them back to his unit.

In July 1919, Duncan managed to bundle the dogs aboard a ship taking him back to the US at the end of the war. When he got to Long Island, New York, for re-entry processing, he put his dogs in the care of a Hempstead breeder named Mrs. Leo Wanner, who raised police dogs. Nanette was diagnosed with pneumonia; as a replacement, the breeder gave Duncan another female German Shepherd puppy. Duncan headed to California by rail with his dogs. While Duncan was traveling by train, Nanette died in Hempstead. As a memorial, Duncan named his new puppy Nanette II, but he called her Nanette. Duncan, Rin Tin Tin, and Nanette II settled at his home in Los Angeles. Rin Tin Tin was a dark sable color and had very dark eyes. Nanette II was much lighter in color.

Rin Tin Tin was much sought after and was signed for endorsement deals. He was featured in ads for Ken-L Ration, Ken-L-Biskit, and Pup-E-Crumbles. Warner Bros. got thousands of requests for publicity photographs of Rinty, which were signed with a paw print and a line written by Duncan: "Most faithfully, Rin Tin Tin." In the 1920s, Rin Tin Tin's success for Warner Bros. inspired several imitations from other studios looking to cash in on his popularity, notably RKO's Ace the Wonder Dog, also a German Shepherd dog. Around the world, Rin Tin Tin was extremely popular, because as a dog, he was equally well understood by all viewers. At the time, silent films were easily adapted for various countries by simply changing the language of the intertitles. Rin Tin Tin's films were widely distributed. By 1927, Rin Tin Tin was the most popular actor with the very sophisticated film audience in Berlin.

Duncan walked his dog up and down Poverty Row, talking to anyone in a position to put Rin Tin Tin in film, however modest the role. The dog's first break came when he was asked to replace a camera-shy wolf in The Man From Hell's River (1922). The wolf was not performing properly for the Director, but under the guidance of Duncan's voice commands, Rin Tin Tin was very easy to work with. When the film was completed, the dog was billed as "Rin Tan". Rin Tin Tin would be cast as a wolf or wolf-hybrid many times in his career because it was much more convenient for filmmakers to work with a trained dog. In another 1922 film titled My Dad, Rin Tin Tin picked up a small part as a household dog. The credits read: "Rin Tin Tin – Played by himself".

Rin Tin Tin's first starring role was in Where the North Begins (1923), playing alongside silent screen Actress Claire Adams. This film was a huge success and has often been credited with saving Warner Bros. from bankruptcy. It was followed by 24 more screen appearances. Each of these films was very popular, making such a profit for Warner Bros. that Rin Tin Tin was called "the mortgage lifter" by studio insiders. A young Screenwriter named Darryl F. Zanuck was involved in creating stories for Rin Tin Tin; the success of the films raised him to the position of respected film Producer. In New York City, Mayor Jimmy Walker gave Rin Tin Tin a key to the city.

Author Susan Orlean investigated the Hollywood legend that Rin Tin Tin received the most votes for Best Actor at the first Academy Award competition in 1929. Orlean says that the Academy wished to appear more serious, that they determined to have a human actor win the award. Rin Tin Tin was removed as a choice and the votes were cast once more: German actor Emil Jannings won the Best Actor award.

Between 1930 and 1955, Rin Tin Tin was cast in three different radio series, beginning April 5, 1930 with The Wonder Dog, in which the original Rin Tin Tin performed some of the sound effects until his death in 1932. (Most of the dog noises were performed live on radio by a man named Bob Barker.) This 15-minute program was broadcast Saturdays on the Blue Network at 8:15 pm until March 1931 when it moved to Thursdays. Story lines were often highly unlikely, with Rin Tin Tin saving a group of space-exploring Scientists from giant Martians in one episode.

Although primarily a star of silent films, Rin Tin Tin did appear in four sound features, including the 12-part Mascot Studios chapter-play The Lightning Warrior (1931), co-starring with Frankie Darro. In these films, vocal commands would have been picked up by the microphones, so Duncan likely guided Rin Tin Tin by hand signals. Rin Tin Tin and the rest of the crew filmed much of the outdoor action footage for The Lightning Warrior on the Iverson Movie Ranch in Chatsworth, Los Angeles, California, known for its huge sandstone boulders and widely recognized as the most heavily filmed outdoor shooting location in the history of the movies.

On August 10, 1932, Rin Tin Tin died at Duncan's home on Club View Drive in Los Angeles. Duncan wrote about the death in his unpublished memoir: He heard Rin Tin Tin bark in a peculiar fashion so he went to see what was wrong. He found the dog lying on the ground, moments away from death. Newspapers across the nation carried obituaries. Magazine articles were written about his life, and a special Movietone News feature was shown to movie audiences. In the press, the death was given a wide variety of fabrications such as Rin Tin Tin dying on the set of the film Pride of the Legion (where Rin Tin Tin Jr. was working), dying at night, and dying at home on the front lawn in the arms of Actress Jean Harlow, who lived on the same street. In a private ceremony, Duncan buried Rin Tin Tin in a bronze casket in his own backyard with a plain wooden cross to mark the location. Duncan was suffering the financial effects of the Great Depression and could not afford a finer burial, nor even his own expensive house. He sold his house and quietly arranged to have the dog's body returned to his country of birth for reburial in the Cimetière des Chiens et Autres Animaux Domestiques, the famous pet cemetery in the Parisian suburb of Asnières-sur-Seine.

In September 1930, the title changed from The Wonder Dog to Rin Tin Tin. Don Ameche and Junior McLain starred in the series, which ended June 8, 1933. With Ken-L Ration as a sponsor, the series continued on CBS from October 5, 1933 until May 20, 1934, airing Sundays at 7:45 pm.

Rin Tin Tin Jr. died in December 1941, at the age of eight, of pneumonia.

Rin Tin Tin finds mention in Anne Frank's diary in her second entry on June 14, 1942. Frank wishes she had a dog like Rin Tin Tin. She also wrote about the 1924 Rin Tin Tin silent film The Lighthouse by the Sea which she and her school friends watched together in her house for her birthday party. According to her the movie was a big hit with her friends.

Rin Tin Tin III starred alongside a young Robert Blake in 1947's The Return of Rin Tin Tin but is primarily credited with assisting Duncan in the training of more than 5,000 dogs for the World War II war effort at Camp Hahn, California.

Duncan groomed Rin Tin Tin IV for the 1950s television series The Adventures of Rin Tin Tin, but the dog performed poorly in a screen test and was replaced in the TV show by trainer Frank Barnes's dogs, primarily one named Flame Jr., called JR, with the public led to believe otherwise. Instead of shooting episodes, Rin Tin Tin IV stayed at home in Riverside, California. The TV show Rin Tin Tin was nominated for a PATSY Award in 1958 and in 1959, but did not win.

The Adventures of Rin Tin Tin, an ABC television series, ran from October 1954 to May 1959. Duncan's Rin Tin Tin IV was nominally the lead dog, but nearly all of the screen work was performed by a dog named Flame Jr., nicknamed JR (pronounced Jay Are), owned by trainer Frank Barnes. Other dogs that sometimes played TV's Rin Tin Tin included Barnes's dog Blaze and Duncan's dog Hey You from the Rin Tin Tin bloodline. Hey You had suffered an eye injury during his youth; he was used as a stunt dog and for fight scenes. TV's Rin Tin Tin was far lighter in color than the original sable-colored dog of silent film.

The final radio series was broadcast on Mutual from January 2, 1955 to December 25, 1955 a 30-minute program heard Sunday evenings. Sponsored by National Biscuit for Shredded Wheat and Milk-Bone, the series featured Rin Tin Tin's adventures with the 101st Cavalry in the same manner as the concurrent TV show: The Adventures of Rin Tin Tin. The radio show also starred Lee Aaker (born 1943) as Rusty, James Brown (1920–1992) as Lieutenant Ripley "Rip" Masters and Joe Sawyer (1906–1982) as Sergeant Biff O'Hara.

Lee Duncan died on September 20, 1960, without ever having trademarked the name "Rin Tin Tin". The tradition continued in Texas with Jannettia Brodsgaard Propps, who had purchased several direct descendant dogs from Duncan. Her granddaughter, Daphne Hereford, continued the lineage and the legacy of Rin Tin Tin following her grandmother's death on December 17, 1988. Hereford passed the tradition to her daughter, Dorothy Yanchak in July 2011. The current Rin Tin Tin is twelfth in line from the original silent film star and makes personal appearances across the country to promote responsible pet ownership. Rin Tin Tin was the recipient of the 2011 American Humane Association Legacy award and was honored by the Academy of Arts and Sciences in a special program, Hollywood Dogs: From Rin Tin Tin to Uggie, on June 6, 2012, at the Samuel Goldwin Theatre. Rin Tin Tin continues to make personal appearances across the country and works in film and other ventures.

In 1976, a film was produced loosely based on Rin Tin Tin's debut: Won Ton Ton, the Dog Who Saved Hollywood. Producer David V. Picker offered a fee to Herbert B. Leonard but Leonard disagreed with the basic premise of a film ridiculing the famous dog. Leonard sued the filmmakers for infringement on the Rin Tin Tin legacy and lost.

Originally co-produced by Leonard, the 1988–93 Canadian TV series Katts and Dog featured the adventures of a police officer and his canine partner. The series was titled Rin Tin Tin: K9 Cop for its American showings, and in France it was presented as Rintintin Junior. Leonard was funded by the Christian Broadcasting Network whose founder, televangelist Pat Robertson, had been enthusiastic for the idea. Leonard was criticized by his fellow producers for staying with his new wife in Los Angeles rather than helping with the show on location in Canada. Partway through the first season, Robertson said that some of his viewers were deeply concerned that the plot involved a widowed mother who was living unmarried in the same house with the brother of her late husband. Robertson recommended the mother character be killed off to stop the complaints, but Leonard protested such a change. After Leonard quit the show the problematic character was killed off. Though separated from the show, Leonard continued to receive a fee for the screen rights to Rin Tin Tin.

In 2007, a children's film was produced—Finding Rin Tin Tin—based on the story of Lee Duncan finding Rin Tin Tin on a battlefield in France and making a star of him in Hollywood. The film was the subject of a lawsuit brought in October 2008 by Daphne Hereford who asked a federal court in Houston, Texas, to protect her rights to the Rin Tin Tin trademark. The judge ruled in favor of the filmmakers, declaring the use of the name in the film to be fair use.

In October 2011 at the first annual American Humane Association Hero Dog Awards in Beverly Hills, Rin Tin Tin was honored with the first Hero Dog Legacy Award. Mickey Rooney narrated a memorial tribute film about Rin Tin Tin. A twelfth-generation Rin Tin Tin legacy dog was there to receive the award.