- Was considered a gifted athlete in high school and showed off his basketball skills in the 1945 film Here Come the Co-Eds, in which he performed his own trick shots.
- Dropped out of high school and moved to California to become an actor. His athletic abilities landed him occasional jobs performing stunts, but he was primarily a laborer.
- Moved to New York in the early 1930s and began performing in vaudeville and burlesque theaters.
- Teamed up formally with Bud Abbott in 1936 after crossing paths several times in burlesque theaters in the early 1930s.
- Received first national exposure with Abbott on the Kate Smith Hour radio show in 1938.
- Along with Abbott, signed by Universal Studios in 1940 to his first film contract for One Night in the Tropics. The duo were not the headliner, but they stole the show with an abbreviated version of their classic bit "Who's On First?"
- Mentioned his hometown of Paterson, NJ in nearly all of the episodes of The Abbott and Costello Show and several of his films. Paterson erected a life-size bronze statue of Costello in 1994.
- Memorialized with Abbott in the National Baseball Hall of Fame and Museum in Cooperstown, NY. They are two of a select few non-baseball players or managers honored with the distinction.
- Was awarded three stars on the Hollywood Walk of Fame for his work in radio, television and film.
- Marie Kirk — Sister
- Pat Costello — Brother
- Anne Battler — Wife
- Christine Costello — Daughter
- Lou Costello Jr. — Son
- Helen Rege — Mother
- Sebastian Cristillo — Father
- Paddy Costello Humphreys — Daughter
- Carole Costello — Daughter
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