She has done voice acting for numerous animated films, television shows, and video games. Her voice roles include Vicky from The Fairly OddParents, Samantha "Sam" Manson from Danny Phantom, Mandy from The Grim Adventures of Billy & Mandy, Frankie Foster, Duchess, and Goo from Foster's Home for Imaginary Friends, Yumi Yoshimura from Hi Hi Puffy AmiYumi, Azula from Avatar: The Last Airbender, Kimiko Tohomiko from Xiaolin Showdown, as well as Lola, Lana, and Lily Loud from The Loud House, and Prince Puppycorn from Unikitty!. She has been the voice of Daphne Blake in the Scooby-Doo cartoons and direct-to-videos and other appearances since 2000 (which she inherited from her friend and teacher Mary Kay Bergman following the latter's suicide). In video games, she voices Amanda Valenciano Libre from Metal Gear Solid: Peace Walker.
DeLisle was born in Fort Ord, California, to truck driver George Van Oosbree and singer Joanna Ruth. Her parents separated when she was young. She has one younger brother. DeLisle's mother became a born-again Pentecostal when she was eleven and she was later raised by her maternal grandmother, Eva Flores, a vocalist who performed with salsa musician Tito Puente. She credits her father's love of country music as the biggest influence on her musical taste. She attended Chula Vista High School in the same graduating class as Mario Lopez. In her late teens, she started singing old gospel tunes, and entered the world of comedy on the advice of a friend. In her comedy routine, DeLisle imitated voices. Her impressions earned the attention of a casting director and was advised to take up voice acting. At this time, she went back to her musical ambitions but also took classes in voice-overs. She soon began working with talent agent Sandy Schnarr. Her first marriage was to Christopher DeLisle in 1992. The two later divorced in 1993. In 2002, she married Murry Hammond of the country band Old 97's; their courtship and wedding were featured in an episode of A Wedding Story. She gave birth to their son Jefferson Texas Hammond in 2007. They divorced in 2010. She later met Jared Griffin through Twitter, and they married on June 27, 2012. Their son, Harlan Roy Griffin, was born in 2014. Griffin gave birth to her third child in 2016, a daughter named Mariposa "Posie" Ruth Griffin.