Jefferies is known for her recurring role as Tracy on the HBO comedy series Eastbound & Down (2009-2010). In 2012, Jefferies was cast in recurring role in the ABC drama series Nashville created by Academy Award winner Callie Khouri. She plays Jolene Barnes, mother of Hayden Panettiere's character, who is a drug addict. She also appeared in films The Notebook, Halloween II, 96 Minutes, and guest starred on One Tree Hill and Surface.