Maria Bello was born on April 18, 1967, one of four children raised in Norristown, Pennsylvania, by a school nurse mother and a construction worker father. She went to Villanova University, where she majored in political science. She had every intention of becoming a lawyer, but she took an acting class during her senior year, just for fun.
She discovered she was very good at acting, and she was soon cast in small, off-Broadway plays, such as The Killer Inside Me, Small Town Gals With Big Problems, and Urban Planning. She later guest-starred on episodes of The Commish, Misery Loves Company, Simon, Nowhere Man, and Due South.
She got her big break when producers Kenny Lenhart and John Sakmar cast her in the spy show Mr. and Mrs. Smith, as Mrs. Smith. Kenny and John had remembered her brilliant performance from a remake of 77 Sunset Strip that never got on its feet. Mr. And Mrs. Smith was abruptly canceled after 8 weeks on the air. Then came a guest role on ER as Dr. Anna Del Amico where Maria guest starred on the final three episodes of the third season, making such a good performance that the producers asked her back as a regular for the series.