Melanie Paxson was born in Champaign, Illinois, and earned a Bachelor of Arts degree in theater from the University of Missouri. Following her academic pursuits, she relocated to Chicago, where she further honed her craft at the renowned Second City and Steppenwolf Theatre.
Paxson's transition to television began with her role in the 1996 series Early Edition, marking her first professional film and television appearance. She then landed a recurring role as "Jaclyn" in the Jeremy Piven series Cupid in 1998. Cupid's success led Melanie to Los Angeles, where she continued to make a name for herself with a string of guest-starring roles in various television shows, including The Drew Carey Show in 1995, Rules of Engagement in 2007, CSI: Crime Scene Investigation in 2000, Joey in 2004, Medium in 2005, and Last Man Standing in 2011.
Paxson's national profile expanded with her work in the Gladware and other commercial campaigns. She also became a regular cast member on shows such as NBC's sitcom Happy Family, where she played "Sara Brennan", the daughter of John Larroquette and Christine Baranski, as well as the harried new mom "Julie" in ABC's series Notes from the Underbelly in 2007.
In December 2013, Melanie Paxson played the role of "Dolly" in the Disney feature Saving Mr. Banks. Her other credits include the telefilm Behind the Camera: The Unauthorized Story of 'Three's Company' in 2003, where she portrayed actress Joyce DeWitt in the unauthorized story of the 1970s sitcom Three's Company. She also appeared in the feature films Ready to Rumble in 2000 and Slackers in 2002.