- Was in a relationship with Jean Harlow for two years before her death and paid for her funeral, costing $30,000. For many years he made sure fresh flowers were always present at her grave.
- In 1938, he was diagnosed with cancer of the rectum. Rather than undergo a colostomy, he agreed to an experimental treatment where platinum needles containing radium pellets were inserted into his body, where they remained for six months, by which time his cancer had gone into remission. It was many years before he publicly revealed he had had cancer. At the time of his illness and recovery, his agent explained his absence to the press first by saying he was recuperating from an eye injury, and later that he had undergone a routine abdominal operation.
- Although he and Carole Lombard divorced in 1933, they remained close friends until her death in 1942.
- His son stabbed himself to death while taking a shower. He left a four-page good-bye letter to his father, with whom he was very close.
- Had difficulties retaining his lines during the filming of Mister Roberts (1955), something that had not happened to him in earlier films; this was one of the reasons why this was his final film appearance. Frail health, including bouts with cancer, plus a difficult Hawaii location shoot ultimately led to his retirement decision.
- If her cameo in The Senator Was Indiscreet (1947) is counted, Myrna Loy co-starred with him 14 times. Besides the six Thin Man films, the others were Manhattan Melodrama (1934), Evelyn Prentice (1934), The Great Ziegfeld (1936), Libeled Lady (1936), Double Wedding (1937), I Love You Again (1940) and Love Crazy (1941).
- Purchased for Jean Harlow a 150-carat sapphire engagement ring for $20,000, and presented it to her for Christmas of 1936.
- He was lured away from Paramount by Warners with a contract of $6000 a week, but after a year or so Jack L. Warner forced Depression salary cuts on many of his stars including Powell, reducing it to $4000 per week. Powell was unhappy with the situation and left Warner for MGM, where he spent the bulk of his career.
- He was the first husband of Carole Lombard while his Manhattan Melodrama (1934) co-star Clark Gable was her second husband.
- He paid $25,000 for a private room in the Great Mausoleum in Forest Lawn Memorial Park where Jean Harlow was laid to rest and where he intended to be buried. However, he married actress Diana Lewis in 1940, remaining with her until his death in 1984 and he was buried in Palm Desert.
- Awarded a star on the Hollywood Walk of Fame for Motion Pictures at 1636 Vine St.
- He and Myrna Loy were so identified as a married couple that, when traveling together, they often had to specifically request separate hotel rooms from mistaken desk clerks.
- Had known Diana Lewis only three weeks when they married 1/6/40.
- His favorite singer was Jo Stafford and he collected every one of her albums.
- He and Casey Stengel were in the same class in Central High School in Kansas City, MO.
- Parent of William Powell with his wife, Eileen.
- Starred in four Oscar Best Picture nominees: The Thin Man (1934), The Great Ziegfeld (1936), Libeled Lady (1936) and Mister Roberts (1955), the first three also co-starred Myrna Loy."The Great Ziegfeld" is the only winner.
- Graduated from the American Academy of Dramatic Arts in 1912 where he studied under Joseph Adelman.
- Produced a Broadway play, "Revolt" in 1928, written by Harry Wagstaff Gribble. It flopped.
- Cousin-in-law of Howard Hawks and Kenneth Hawks.
- His home in Beverly Hills was designed by James E. Dolena and decorated by William Haines.
- His star on the Hollywood Walk of Fame is featured for a brief moment in Kelly Does Hollywood: Part 2 (1991).
- On 8/20/20, he was honored with a day of his filmography during the Turner Classic Movies Summer Under the Stars.
- First actor to portray the character of George Wilson on-screen in The Great Gatsby (1926).
- In May 2023, he was honored as Turner Classic Movies Star of the Month.
- Leo Kottke composed an instrumental song entitled 'William Powell'; the studio version appears on Kottke's 1989 album "My Father's Face", and a live version on 1995's "Leo Kottke Live".
- Brother-in-law of Maxine Lewis and J.C. Lewis.
- Biography in: "The Scribner Encyclopedia of American Lives". Volume One, 1981-1985, pages 652-654. New York: Charles Scribner's Sons, 1998.
- Cousin-in-law of William B. Hawks.
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