Seaton, along with fellow Writer and friend Robert Pirosh, joined Metro-Goldwyn-Mayer as a contract Writer in 1933. His first major screen credit was the Marx Brothers comedy A Day at the Races in 1937. In the early 1940s, he joined 20th Century Fox, where he remained for the rest of the decade, writing scripts for Moon Over Miami, Coney Island, Charley's Aunt, The Song of Bernadette, and others before making his directorial debut with Diamond Horseshoe in 1945. From this point on he was credited as both Screenwriter and Director for most of his films, including The Shocking Miss Pilgrim, Miracle on 34th Street, Apartment for Peggy, Chicken Every Sunday, The Big Lift, For Heaven's Sake, Little Boy Lost, The Country Girl, and The Proud and Profane.
But Not Goodbye, Seaton's 1944 Broadway debut as a Playwright, closed after only 23 performances, although it later was adapted for the 1946 MGM film The Cockeyed Miracle by Karen DeWolf. In 1967 he returned to Broadway to direct the Norman Krasna play Love in E Flat, which was a critical and commercial flop. The musical Here's Love, adapted from his screenplay for Miracle on 34th Street by Meredith Willson, proved to be more successful.
Seaton won the Academy Award for Best Adapted Screenplay twice, for Miracle on 34th Street (which also earned him the Golden Globe Award for Best Screenplay) and The Country Girl, and was nominated for Oscars three additional times. He received The Jean Hersholt Humanitarian Award in 1961. He directed 1970's blockbuster hit Airport, which earned 10 Oscar nominations, including one for Seaton's screenplay.
Seaton died of cancer in Beverly Hills, California in 1979.