Povinelli was born in Elyria, Ohio, and is the youngest of four children. His parents and siblings are average-size. His older brother Brian Povinelli is a marketer who inspired Mark's acting career. He is of Italian descent. Povinelli graduated from Our Lady of Good Counsel High School in Wheaton, Maryland in 1989, and then graduated in 1993 from Miami University with a degree in Mass Communications and a minor in Theater Acting. His repertory encompasses drama, comedy, and fantasy. He has appeared in a wide range of productions, from stage plays by William Shakespeare and Ben Jonson to roles in television series such as Modern Family and Boardwalk Empire, as well as in popular movies including The Polar Express (2004, directed by Robert Zemeckis). Onstage in 2003 in Lee Breuer's production of Henrik Ibsen's A Doll's House, retitled Mabou Mines DollHouse, Povinelli drew praise from The New York Times: "The men embody small-minded convention and stunted possibilities...Mr. Povinelli makes us feel Torvald's repressive sexual virility at every turn." He has characterized his approach to acting for The Village Voice: "Being so tremendously different provides you with an analytical depth ... Like any actor, I try to bring as much of myself to the role I'm playing as possible. Every day I go out I'm made aware of my size. Why should I deny myself the richness of that experience when I go onstage?"
Povinelli starred opposite Robert Pattinson and Oscar winners Reese Witherspoon and Christoph Waltz in the Fox 2011 film, Water for Elephants, playing the role of Kinko. The film was adapted from the NY Times bestseller by Sara Gruen and premiered April 2011.
He appeared in Mirror Mirror (2012), which starred Julia Roberts, Armie Hammer (The Social Network), and Lily Collins. In the same year, Povinelli was cast as a series regular on the television series Are You There, Chelsea?, starring Laura Prepon. This made him the first little person ever to be cast as a series regular on a network studio sitcom.

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