Khloé Alexandra Kardashian was born in Los Angeles, California on June 27, 1984, to parents Robert and Kris (née Houghton). She has two older sisters Kourtney and Kim, and a younger brother Rob. Their mother is of Dutch, English, and Scottish ancestry, while their father was a third-generation Armenian American. After their parents divorced in 1991, Houghton remarried to the 1976 Summer Olympics decathlon winner Bruce Jenner in 1991. Through their marriage, Kardashian gained step-brothers Burton "Burt", Brandon, and Brody; step-sister Casey; and half-sisters Kendall and Kylie. In 1994, her father garnered public attention as the primary defense lawyer for football player O.J. Simpson during his murder trial.

In 2001, Kardashian suffered an traumatic brain injury in an car accident in which she went through the windscreen and suffered a severe concussion, she suffers from long-term memory loss. Khloé has stated "I went through the windscreen and had really bad concussion…and now I can't remember anything…and I think it's getting worse".

On September 27, 2009, Kardashian married NBA basketball player Lamar Odom, who was a member of the Los Angeles Lakers at the time. The couple were married exactly one month after they met at a party for Odom's teammate Metta World Peace. Following her marriage, Kardashian removed her middle name to include her married surname, becoming Khloé Kardashian Odom. Kardashian adopted a pet boxer named Bernard "BHops" Hopkins, after the famous boxer. On December 13, 2013, after months of speculated separation, Kardashian filed for divorce from Odom, and for legal restoration of her last name.

Kardashian was allegedly reported to be an relationship with French Montana as the couple continues to be seen together out sharing romantic actions.]Kardashian's mother denied allegations insisting that Kardashian and Montana are nothing more than just friends. "They're friends. He's a good friend," she said. "They're just hanging out" .They have since confirmed the relationship by taking part in their first interview as a couple with Angie Martienez. During this they discussed French's religion and him observing Ramadan.