- The Powell's lived a few blocks away from the Carpenter's, whose daughter would later be known as Jean Harlow on screen. However, William Powell and Jean Harlow only met for the first time whilst acting.
- William Powell was a classmate of Edward G. Robinson at the American Academy of Dramatic Arts.
- He produced a Broadway play in 1928 called Revolt. Unfortunately it flopped.
- W.S. Van Dyke was given only three weeks to film The Thin Man. They finished filming after sixteen days.
- In 1938, Powell was diagnosed with rectal cancer. Instead of going through a colostomy he had experimental treatment where radium pellets were inserted into his body. They remained there for six months, eventually ending the cancer. He did not continue acting until a year later.
- Alfred Hitchcock wanted William Powell to play the leading roles in Rebecca and Shadow of a Doubt, the parts were taken by Laurence Olivier and Joseph Cotten instead.
- During filming The Thin Man, between takes, William playfully began shooting Christmas decorations with an air gun. W.S. Van Dyke loved this and decided to use it in the film.
- There are only two talkie films in which Powell didn't have a moustache: Shadow of the Law and Love Crazy. In Shadow of the Law it is for the prison scene, and in Love Crazy it is when he dresses up to impersonate Myrna Loy's aunt.
