- His mum named him after actor John Saxon.
- Moved to America when he was four years old.
- Grew up in the Jackson Heights section of Queens, New York.
- Parents divorced when he was thirteen.
- Was voted most "Most Talkaktive" in Murray Bergtrum High School.
- He got arrested for truancy when he tried to sneek into a porn film at Times Square together with some friends. He also got arrested for breaking in a subway door and commandeering the microphone.
- Was accepted into the Lee Strasburg Actors Studio, but only studied with the master himself for one day before he died during the night. "I have that affect on people," Leguizamo quipped.
- Is a fan of "Rescue Me", "Californication", "Mad Men" and "Weeds".
- His favourite play is "Long day's journey into night".
- Worked at Kentucky Fried Chicken in order to pay for his acting classes.
- His very first movie was a studentfilm called "Five out of six" directed by Daniel Taplitz which won a Spielberg Focus Award.
- Good friends with actor Luis Guzmán.
- He had a parrot named Homey and a cat named Coochie together with ex wife Yelba Osorio.
- According to his autobiography he accidently stole Samantha Mathis from Nicolas Cage, and later River Phoenix stole Samantha from him.
- Got drunk for the first time when he was thirteen.
- Lost his virginity when he was sixteen.
- His brother Sergio fell ill off osteomylitis and was pharalayzed for a couple of years.
- John proposed to Justine in the deep jungles of Mexico.
- Uses glasses and contact linses.
- Met ex wife Yelba Osorio at a comedy workshop.
- Named his son Ryder Lee after Bruce Lee.
- Turned down the part of Tom Hanks lover Miguel in "Philadelphia".
- Has a production company called Rebel Films.
- He is a recovering Catholic.
- Good friends with Rosie Perez.
- Loves to dance.
- The chain that John often wears around his neck he had specially made in Mexico City while filming "Romeo + Juliet".
- Always watches his takes in the monitor after each scene to correct his mistakes.
- Have known actor Freddy Rodriguez since Freddy was in high school.
- His favorite horror films are "Night of the Living Dead" and "The Exorcist".
- Listed as one of twelve "Promising New Actors of 1991" in John Willis' Screen World, Vol. 43.
- He is a democrat.
- His idols in stand up are Lily Tomlin and Richard Pryor.
- His favorite genre to do is drama.
- Likes to do a lot of takes.
- Is a fan off 60's and 70's movies.
- Some of his favorite movies are "Annie Hall" and "Mean Streets".
- Often gets mistaken for singer Marc Anthony.
- He quit smoking July 23, 2008.