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

In 2001, Kardashian suffered a traumatic brain injury in a car accident. She went through the windscreen and suffered a severe concussion, causing long-term memory loss.

On March 4, 2007, Kardashian was arrested for driving under the influence. On July 18, 2008, Kardashian turned herself in and reported to jail to serve time for violation of probation. She faced a sentence of up to 30 days and enrollment in an alcohol treatment program within three weeks of her release from jail. She was released from jail fewer than three hours later due to overcrowding.

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.

The sisters also released a book, Kardashian Konfidential, in November 2010. In February 2011, Kardashian and her husband released a unisex fragrance called "Unbreakable." In May 2011, Kardashian and her sisters announced the release of their first novel. Prior to publication, the sisters requested help with naming their book. The winner was offered a cameo appearance in the novel. In July 2011, it was announced that the winning title was "Dollhouse". In October 2012, Kardashian and Odom released a second unisex fragrance called "Unbreakable Joy," inspired by the holiday season.

In December 2011, Kardashian was sued by a woman who claimed Kardashian and 10 other people assaulted her outside a nightclub in December 2009.

In March 2012, Kardashian and her sisters Kourtney and Kim were named in a $5 million class action lawsuit against QuickTrim, the weight loss supplement they endorse. The complaint, filed in the United States District Court for the Southern District of New York, accuses the Kardashians (along with QuickTrim's manufacturer, Windmill Health Products; the retailer GNC; and others in the sales and marketing chain) of false and deceptive marketing of the diet aid. The plaintiffs, hailing from several states, brought claims under their respective states' consumer protection laws.

On December 13, 2013, after months of speculated separation, Kardashian filed for divorce from Odom and for legal restoration of her last name. Divorce papers were signed by both parties in July 2015; however, the divorce had yet to receive final approval from a judge. In October 2015, Odom was hospitalized after being found unconscious in a Nevada brothel, and was in a coma for four days; as he lay in a hospital, Kardashian withdrew her pending divorce petition. In an interview with People Magazine, Kardashian confirmed that they had not reconciled and the divorce had been withdrawn so that she might make medical decisions on Odom's behalf. Kardashian and Odom's divorce was finalized in December 2016.

Kardashian supports the recognization of the Armenian Genocide and has visited the memorial of the victims in Yerevan, Armenia. In April 2015, Kardashian accompanied her sister, Kim, and brother-in-law, Kanye West, to Jerusalem for the baptism of her niece, North, in the Armenian Apostolic Church at the Cathedral of St. James. She was named North's godmother during the ceremony.

In 2016, she hosted her own talk show, Kocktails with Khloé, and stars in the health and fitness docu-series Revenge Body with Khloé Kardashian.

Kardashian is currently in a relationship with basketball player Tristan Thompson. The couple reside in Cleveland, Ohio. In December 2017, she announced they were expecting their first child together. In March 2018, Kardashian revealed she would have a girl. On April 12, Kardashian gave birth to their daughter.