Born Andrea Kay Pyle in Houston, TX, a six-month-old Pyle was given the fateful nickname of "Little Missi," which would stick to her throughout her childhood and to the present day. Pyle was infatuated with acting by the age of 13, and attended Germantown High School in Tennessee, one of the top three performing-arts high schools in the United States. While there, Pyle was tapped as a lead singer in several musical productions, though her eventual goal remained a career in television and film. After graduation from Germantown High, Pyle was accepted to the prestigious North Carolina School of the Arts and was cast as the female lead in a series of Shakespearean productions. During the summer, she crossed the Atlantic to attend the Oxford School of Drama in England, where she further honed her acting skills.
By 1996, Pyle had made her film debut in The Cottonwood, which followed a group of wannabe actors hoping to use their lottery winnings to score big in Hollywood. Pyle's breakout role, however, wouldn't come until several years later, when she played a supporting role as a love-struck alien in Galaxy Quest alongside Tim Allen and Sigourney Weaver. Though the early 2000s did little to bring Pyle much in the way of mainstream success, they nonetheless helped the actress develop a loyal fan base; her performances in The Wayne Brady Show, Ally McBeal, and Josie and the Pussycats (all 2001) were solid enough to grab the attention of several prominent casting directors. Surely enough, by 2003, Pyle had been chosen for a supporting role in Bringing Down the House with Steve Martin and Queen Latifah, as well as a small but indelible role in Tim Burton's big-budget fantasy comedy Big Fish (2003). In 2004, Pyle worked with Ben Stiller in Along Came Polly and lent her support to Soul Plane and 50 First Dates. Working with Stiller proved a lucky experience for Pyle, who accepted a larger supporting role in Stiller's Dodgeball: A True Underdog Story (2004), which also stars fellow Galaxy Quest alumni Justin Long. When she isn't filming, Pyle continues her work with the all-female sketch comedy group Bitches and Funny.