[5] Having achieved poor grades at his school, Haberdashers' Aske's Hatcham College,[6] he left to become an actor and joined the National Youth Theatre at 15.

After being perennially cast in "fat" roles, he lost 77 lbs (35 kg) at age 19, which brought more acting opportunities.

[5] Spall has frequently collaborated with Edgar Wright, appearing in his films Shaun of the Dead, Hot Fuzz and The World's End alongside Simon Pegg and Nick Frost.

In 2012, Spall portrayed Canadian author Yann Martel in the Academy Award-winning drama film Life of Pi, directed by Ang Lee.

[8] In 2014, Spall appeared in the coming-of-age drama X+Y, alongside Asa Butterfield and Sally Hawkins, and the seasonal family comedy Get Santa.

In 2015, he played John Hancock in the History Channel three-part series, Sons of Liberty, alongside Jim Broadbent, and appeared in the Academy Award-winning biographical comedy-drama The Big Short, alongside Christian Bale, Brad Pitt, Ryan Gosling and Steve Carell.

[13] In February 2008, Spall met actress Elize du Toit; they were married on 14 August 2010[14] and lived in West Kensington, London.