In 1912 Stone found great success in the popular play Bird of Paradise which starred Laurette Taylor. The play was later filmed in 1932 and 1951. Stone's career was interrupted by World War I. By then he had a white-haired, distinguished appearance and began appearing in roles which matched his demeanor. He showed up in First National's 1920 Nomads of the North (a wonderfully preserved silent film) to good effect playing a Royal Canadian Mounted Policeman. He portrayed the title role in the 1922 silent film version of The Prisoner of Zenda, as well as THE ROLE OF "Rudolf Rassendyll".
Stone was nominated for the Academy Award for Best Actor in 1929 for The Patriot. After that, he appeared in seven films with Greta Garbo, spanning both the silent and early sound periods. He played the role of Dr. Otternschlag in the Garbo film Grand Hotel, in which, completely unaware of all the high drama that has just occurred, he utters the famous closing line: "Grand Hotel. People come. People go. Nothing ever happens". He played a larger role in the 1933 Garbo film Queen Christina. His appearance in the highly successful prison film The Big House furthered his career, and he starred with some of the biggest names in Hollywood in the 1930s, such stars as Norma Shearer, John Gilbert, Ramón Novarro, Clark Gable, andJean Harlow.
He played adventurers in the dinosaur epic The Lost World (1925) with Wallace Beery and The Mask of Fu Manchu (1932) with Boris Karloff, and a police captain in Bureau of Missing Persons (1933). In 1937 Stone essayed the role which would become his most famous, that of Judge James Hardy in the Mickey Rooney "Andy Hardy" series. Stone appeared as the judge in fifteen movies, beginning with You're Only Young Once (1937).
Stone died in Hancock Park on September 12, 1953, aged 73. Stone reportedly suffered a heart attack while chasing away some neighborhood kids who were throwing rocks at his garage. Another published report states that on that date Stone and his third wife were watching television when they heard a racket in the back yard. When he investigated, Stone found lawn furniture once again floating in the pool and glimpsed three or perhaps four teenage boys running towards the street. Stone gave chase despite his wife’s warning not to exert himself. Upon reaching the sidewalk, Stone suddenly collapsed. A gardener, Juan Vergara, witnessed the chase and summoned aid.
A published photo circulated in newspapers of the day, showed Stone's body on the sidewalk, immediately after the incident. Decades later, the photo was later published in Kenneth Anger's Hollywood scandals book, Hollywood Babylon .
Lewis Stone was later honored with a star on the Hollywood Walk of Fame at 6524 Hollywood Blvd.