His work was admired by stage actress Ethel Barrymore and she wore his clothes for several of her stage productions. He also designed Katharine Hepburn's wardrobe for her Broadway debut in "Death Takes a Holiday" and costumes for the St Louis Opera Company.
It was old friend Cary Grant who introduced him to the Head of Wardrobe at Warner Brothers and he would go on to work there from 1932 to 1944. His created costumes with a philosophy that "characters should dictate clothes, not the other way around". He used a wide range of greys and fabrics of high quality and enhanced with intricate detail. The kind of details he would use included; tiny pleating, piping, which created subtle surface shadows, embroidery, crocheted lace and sometimes handpainted fabrics. He would also spice things up sometimes by using polka dots and rows of buttons.
He had a reputation for being brilliant and a perfectionist but very difficult to work with. He had a tense relationship with studio chief Jack L. Warner, which was compounded by his alcoholism. Orry-Kelly designed costumes for gangster movies, costume dramas and musicals. His period costumes were noted for their authenticity and richness.
He designed and dressed for such actresses as: Bette Davis, Olivia de Havilland, Ava Gardner, Katharine Hepburn and Barbara Stanwyck. Some of his best designs can be seen in Jezebel (1938), The Maltese Falcon (1941), Casablanca (1943), An American in Paris (1951), Les Girls (1957) and Some Like It Hot (1959).
Costume designer Walter Plunkett, one of the best in the business, once referred to his colleague Orry-Kelly as "the greatest of all Hollywood designers."