After several supporting roles, she was a lead performer in such films as Thousands Cheer (1943), Anchors Aweigh (1945) with Frank Sinatra and Gene Kelly and Show Boat (1951) and Kiss Me Kate (1953), both with Howard Keel.

Grayson's sister Frances Raeburn (born Mildred Hedrick) was also an actress and singer, appearing along with her in the film Seven Sweethearts.

Two further films were planned for Grayson in 1941: White House Girl,[8] which was later produced in 1948 with Durbin,[9] and Very Warm for May, from the Jerome Kern and Oscar Hammerstein musical of the same name.

[13] In 1943, Grayson appeared in the film Thousands Cheer, (originally titled Private Miss Jones), along with Gene Kelly, Mickey Rooney, Eleanor Powell, June Allyson and others.

[citation needed] Grayson did not appear in any films for nearly two years (from 1943 to 1945), but instead worked at entertaining troops during the war and performing on radio programs.

[16] She returned to films in Anchors Aweigh, a musical romantic-comedy set in Los Angeles and co-starring Kelly and Frank Sinatra.

Her performance in Till the Clouds Roll By included "Make Believe" in a capsule version of the musical Show Boat, which would be remade five years later, with Grayson in the starring role.

[citation needed] In 1950, Grayson was once again partnered with Lanza, and portrayed an opera singer in The Toast of New Orleans, and performed the Academy-Award-nominated song "Be My Love".

[21] She portrayed an opera singer with laryngitis, alongside Van Johnson who played her doctor and love interest.

[citation needed] Grayson was next cast as Magnolia Hawks in the 1951 remake of the 1927 Hammerstein and Kern musical, Show Boat.

She returned to co-star for a third time with Howard Keel in her most acclaimed role, as Lilli Vanessi/Katharina in Kiss Me Kate, released in November 1953.

[citation needed] While on loan to Warner Bros, her first musical release was The Desert Song, May 1953, alongside Gordon MacRae.

[citation needed] Grayson appeared on television occasionally, having guest starred in the CBS anthology series, General Electric Theater in the episode, Shadow on the Heart, with John Ericson, and on Playhouse 90 in the title role of the "Lone Woman", with Raymond Burr and Scott Brady in the historical roles of the brothers Charles and William Bent, respectively.

Grayson appeared on stage in numerous productions including Show Boat, Rosalinda, Kiss Me, Kate, Naughty Marietta, and The Merry Widow, for which she was nominated for Chicago's Sarah Siddons Award.

In 1953, Grayson optioned the story It's Greek to Me, written by Helen Deutsch, to be accompanied by a score from Cole Porter.

She then continued the role for over sixteen months in the national tour of the United States before leaving for health reasons.

Her dramatic and comedy stage roles included Night Watch, Noises Off, Love Letters and Something's Afoot as Dottie Otterling.

"[28] In 1952, Grayson was offered more than $10,000 to perform for a week at the Riviera night club in New Jersey before making The Desert Song.

[citation needed] Grayson supervised the Voice and Choral Studies Program at Idaho State University.