Kendra Wilkinson was born in San Diego, the elder of two children. She grew up in Clairemont, a middle-class community in central San Diego, and attended Clairemont High School, from where she graduated in 2003. She played softball for six years with the Clairemont Bobby Sox. When she left high school she began working as a glamour model, and also briefly worked as an office assistant for a dentist. Her family resides in San Diego.

Wilkinson met Hefner at his 78th birthday party in April 2004, where she had been hired to be one of the "painted girls": women who are completely nude except for painted-on accessories. Apparently he had seen her picture, shot by photographer Kim Riley, on a fax machine at the Playboy Mansion and wanted to know who she was. Shortly after they met, Hefner asked Kendra to be one of his girlfriends and he moved her into the Playboy Mansion.

Wilkinson has made several cameos on different programs such as Las Vegas, Entourage and Curb Your Enthusiasm. She also appeared in Akon's music video "Smack That". While on the set of the video, Eminem poured a bottle of water on her head, sparking an altercation. The incident was discussed on The Girls Next Door. Kendra also showed her creative side as a rapper on MTV's Celebrity Rap Superstar which debuted on August 30, 2007.

Her stated career goal is to become a massage therapist or sports announcer. As of December 2005, she has become a regular "blogger" columnist at the website of the Philadelphia Eagles, the team for which her mother had been a professional cheerleader.

She is featured on the E! reality television series The Girls Next Door, which follows the lives of Hefner's current girlfriends. Wilkinson lives in her own room in Hefner's mansion with her dogs, Raskal and Martini. In 2006, she appeared in the Playboy Special Editions Sexy 100.

In 2007, she appeared in Nickelback's music video of "Rockstar", along with Girls Next Door co-stars, Holly Madison and Bridget Marquardt.