Clark, 67, and son Ariel Hanrath-Clark, 22, were killed in Pacific Palisades, said Lyne Leavy, Clark's personal assistant.
The two men were in an Infiniti that collided on Pacific Coast Highway with a GMC Yukon around 2:30 a.m., said Lt. Paul Vernon, a police spokesman.
The driver of the other vehicle, Hector Velazquez-Nava, 24, of Los Angeles and his passenger, described as a 29-year-old woman, were taken to UCLA Medical Center with minor injuries.
The driver remained hospitalized and will be booked for investigation of "gross vehicular manslaughter" after being treated, Vernon said.
Photos: "A Christmas Story"
"The initial investigation has concluded that Nava was driving without a license northbound in the southbound lanes while under the influence of an alcoholic beverage," Vernon said.
Nava's passenger was released from the hospital after receiving treatment.
In Clark's most famous film, all 9-year-old Ralphie Parker wants for Christmas is an official Red Ryder carbine-action 200-shot range model air rifle.
His mother, teacher and Santa Claus all warn: "You'll shoot your eye out, kid."
A school bully named Scut Farkus, a leg lamp, a freezing flagpole mishap and some four-letter defiance helped the movie become a seasonal TV fixture with "It's a Wonderful Life" and "Miracle on 34th Street."
Clark specialized in horror movies and thrillers early in his career, directing such 1970s flicks as "Children Shouldn't Play With Dead Things," "Murder by Decree," "Breaking Point" and "Black Christmas," which was remade last year.
His breakout success came with the 1981 sex farce "Porky's," a coming-of-age romp that he followed two years later with "Porky's II: The Next Day."
In 1983, "A Christmas Story" marked a career high for Clark. Darrin McGavin, Melinda Dillon and Peter Billingsley starred in the adaptation of Jean Shepard's childhood memoir of a boy in the 1940s.
The film was a modest theatrical success, but critics loved it.
In 1994, Clark directed a forgettable sequel, "It Runs in the Family," featuring Charles Grodin, Mary Steenburgen and Kieran Culkin in a continuation of Shepard's memoirs.
In recent years, Clark made family comedies that were savaged by critics, including "Karate Dog," "Baby Geniuses" and its sequel, "Superbabies: Baby Geniuses 2."
Among Clark's other movies were Sylvester Stallone and Dolly Parton's "Rhinestone," Timothy Hutton's "Turk 182!", and Gene Hackman and Dan Aykroyd's "Loose Cannons."