Luke made his film debut in The Painted Veil (1934), and the following year gained his first big role, as Charlie Chan's eldest son in Charlie Chan in Paris.
He worked so well with Warner Oland, the actor playing Chan, that "Number One Son" became a regular character in the series, alternately helping and distracting 'Pop' Chan in each of his murder cases.
Luke appeared seven times as Lee Chan opposite Oland's Chan.
Keye Luke left the Charlie Chan series in 1938, shortly after Oland died.
The unfinished Oland-Luke film Charlie Chan at the Ringside was completed as Mr. Moto's Gamble, with Luke now opposite Peter Lorre.

Unlike some performers who failed to establish themselves beyond a single role, Keye Luke continued to work prolifically in Hollywood, at several studios.
Metro-Goldwyn-Mayer cast him in a recurring role in its Dr. Kildare film series, and Monogram Pictures featured him in its Frankie Darro comedies and starred him as Mr. Wong in Phantom of Chinatown.
Unlike Boris Karloff, who had preceded him in the Mr. Wong role, Luke played the detective without any exotic touches.
Though his Mr. Wong was of Chinese descent and able to speak Chinese, he was otherwise an ordinary American gumshoe, with no trace of a foreign accent or "Oriental" philosophy.

RKO Radio Pictures used Luke in its popular adventures of The Falcon and Mexican Spitfire.
Luke also worked at Universal Pictures, where he played two-fisted valet/chauffeur Kato in its Green Hornet serials.
In 1946 Universal mounted a low-budget serial consisting largely of action footage from older films; Keye Luke was hired to match old footage of Sabu in the serial Lost City of the Jungle.

In 1948, Keye Luke returned to the Chan mysteries, which were now being produced by Monogram and starred Roland Winters as Chan. "
Number One Son" appeared in the last two Chan features, The Feathered Serpent along with "Number Two Son" Tommy Chan (Victor Sen Yung) in their only appearance together, and Sky Dragon.
In both of these films, Luke was older than the actor playing his father.
Luke had a featured Broadway role in the Rodgers and Hammerstein musical Flower Drum Song, directed by Gene Kelly in 1958.
The soundtrack album captures his singing of the part of Mr. Wang, the family patriarch.

Luke continued to play character parts in motion pictures.
He had a featured role in The Chairman (1969) starring Gregory Peck.
He provided the voice of the evil Mr. Han in Enter the Dragon (1973) starring Bruce Lee.
Luke played the mysterious old Chinatown shopowner Mr. Wing in the two Gremlins movies and he had a significant role in Woody Allen's 1990 movie Alice.

Keye Luke also worked extensively in television, making numerous guest appearances, including four on The F.B.I. and seven TV movies.
He was a regular cast member in two short lived sitcoms, Anna and the King (1972) starring Yul Brynner and Sidekicks (1986–87). "
Number One Son" ascended to the role of Charlie Chan himself, thus becoming the first actor of Chinese descent to play the role: he supplied the voice of "Mr. Chan" in the animated television series The Amazing Chan and the Chan Clan (1972).

He was also known for his role of Master Po in the television series Kung Fu (1972–75).
In 1985, Luke played 'The Ancient One' on the soap opera General Hospital, for the Asian Quarter storyline, which showcased strong chemistry between Luke and young actress Kimberly McCullough, whom he mentored.
 In 1986, Luke appeared in season two of "The Golden Girls" as Sophia's love interest.
Additionally Luke voiced many animated series including Brak in Space Ghost, the aforementioned  Charlie Chan, and Zoltar/The Great Spirit/Colonel Cronus in Battle of the Planets.

Luke played Governor Donald Cory in an episode of the original Star Trek entitled "Whom Gods Destroy" (1969), and was going to play Doctor Noonien Soong in the Star Trek: The Next Generation episode "Brothers" but illness prevented him from doing so; Brent Spiner ultimately took over the role.

In the Fractured Fairy Tales episode "The Enchanted Fly," one of the rewards offered
Luke made his film debut in The Painted Veil (1934), and the following year gained his first big role, as Charlie Chan's eldest son in Charlie Chan in Paris. He worked so well with Warner Oland, the actor playing Chan, that "Number One Son" became a regular character in the series, alternately helping and distracting 'Pop' Chan in each of his murder cases. Luke appeared seven times as Lee Chan opposite Oland's Chan. Keye Luke left the Charlie Chan series in 1938, shortly after Oland died. The unfinished Oland-Luke film Charlie Chan at the Ringside was completed as Mr. Moto's Gamble, with Luke now opposite Peter Lorre.
Unlike some performers who failed to establish themselves beyond a single role, Keye Luke continued to work prolifically in Hollywood, at several studios. Metro-Goldwyn-Mayer cast him in a recurring role in its Dr. Kildare film series, and Monogram Pictures featured him in its Frankie Darro comedies and starred him as Mr. Wong in Phantom of Chinatown. Unlike Boris Karloff, who had preceded him in the Mr. Wong role, Luke played the detective without any exotic touches. Though his Mr. Wong was of Chinese descent and able to speak Chinese, he was otherwise an ordinary American gumshoe, with no trace of a foreign accent or "Oriental" philosophy.
RKO Radio Pictures used Luke in its popular adventures of The Falcon and Mexican Spitfire. Luke also worked at Universal Pictures, where he played two-fisted valet/chauffeur Kato in its Green Hornet serials. In 1946 Universal mounted a low-budget serial consisting largely of action footage from older films; Keye Luke was hired to match old footage of Sabu in the serial Lost City of the Jungle.
In 1948, Keye Luke returned to the Chan mysteries, which were now being produced by Monogram and starred Roland Winters as Chan. "Number One Son" appeared in the last two Chan features, The Feathered Serpent along with "Number Two Son" Tommy Chan (Victor Sen Yung) in their only appearance together, and Sky Dragon. In both of these films, Luke was older than the actor playing his father. Luke had a featured Broadway role in the Rodgers and Hammerstein musical Flower Drum Song, directed by Gene Kelly in 1958. The soundtrack album captures his singing of the part of Mr. Wang, the family patriarch.
Luke continued to play character parts in motion pictures. He had a featured role in The Chairman (1969) starring Gregory Peck. He provided the voice of the evil Mr. Han in Enter the Dragon (1973) starring Bruce Lee. Luke played the mysterious old Chinatown shopowner Mr. Wing in the two Gremlins movies and he had a significant role in Woody Allen's 1990 movie Alice.
Keye Luke also worked extensively in television, making numerous guest appearances, including four on The F.B.I. and seven TV movies. He was a regular cast member in two short lived sitcoms, Anna and the King (1972) starring Yul Brynner and Sidekicks (1986–87). "Number One Son" ascended to the role of Charlie Chan himself, thus becoming the first actor of Chinese descent to play the role: he supplied the voice of "Mr. Chan" in the animated television series The Amazing Chan and the Chan Clan (1972). 
He was also known for his role of Master Po in the television series Kung Fu (1972–75). In 1985, Luke played 'The Ancient One' on the soap opera General Hospital, for the Asian Quarter storyline, which showcased strong chemistry between Luke and young actress Kimberly McCullough, whom he mentored.  In 1986, Luke appeared in season two of "The Golden Girls" as Sophia's love interest. Additionally Luke voiced many animated series including Brak in Space Ghost, the aforementioned  Charlie Chan, and Zoltar/The Great Spirit/Colonel Cronus in Battle of the Planets.
Luke played Governor Donald Cory in an episode of the original Star Trek entitled "Whom Gods Destroy" (1969), and was going to play Doctor Noonien Soong in the Star Trek: The Next Generation episode "Brothers" but illness prevented him from doing so; Brent Spiner ultimately took over the role.
In the Fractured Fairy Tales episode "The Enchanted Fly," one of the rewards offered 
Keye Luke