From 2010 to 2016, Mixon starred as Victoria Flynn, sister to Melissa McCarthy's character, on the CBS sitcom Mike & Molly.

[4][5] Mixon made her motion picture debut in the 2005 thriller film The Quiet starring Elisha Cuthbert, playing the character Michelle Fell.

[10][11] In 2010, Mixon was cast as Victoria Flynn in the CBS comedy series Mike & Molly opposite Melissa McCarthy and Swoosie Kurtz.

During her time on Mike & Molly, Mixon co-starred alongside Jessica Chastain and Michael Shannon in the critically acclaimed independent drama film Take Shelter which was released in 2011.

In 2016, she appeared alongside Jeff Bridges and Chris Pine in the critically acclaimed crime film Hell or High Water.

[14] In 2016, Mixon was cast in the first leading role of her career on the ABC comedy series American Housewife created by Sarah Dunn.