Joshua Michael Homme was born in Joshua Tree, California on May 17, 1973. He grew up in an affluent family in Palm Desert, California. His paternal grandfather, Cap, moved to the area from North Dakota. Homme's surname is of Norwegian origin and is believed to come from the town of Valle.

On December 3, 2005, Homme married singer and musician Brody Dalle of The Distillers. They reside in Palm Springs, California with their daughter, Camille Harley Joan Homme (born January 17, 2006), and two sons, Orrin Ryder Homme (born August 12, 2011) and Wolf Dillon Reece Homme (born February 13, 2016).  Homme has over 20 tattoos. On his knuckles, he has his grandparents' nicknames ("Cam" for "Camille" on the left and "Cap" on the right) with hearts and his two sons' names ("ORH" for "Orrin Ryder Homme" and "Wolf"). He has his daughter's name, also Camille, tattooed over his heart. His left arm has a switchblade with "Stay Sharp" underneath, while his inner right arm has a straight-edge razor with "Born to Win" inscribed; underneath, his nickname, "Baby Duck", is a shared tattoo with his Eagles of Death Metal bandmate Jesse Hughes, who has his nickname "Boots Electric" in the same location. Homme also shares a tattoo that says "Freitag 4:15" with former Queens of the Stone Age bandmates Nick Oliveri and Mark Lanegan and their sound engineer Hutch, commemorating their "worst show ever" at the Rock Am Ring Festival in Germany on Friday, June 1, 2001, at 4:15 pm. They all got the tattoo on their ribs so that it would hurt the most and serve as a reminder.  Homme has described himself as "very politically conservative" and "very socially liberal", considering himself a "fallen libertarian". He owns several guns, including a classic Winchester rifle, a sawed-off shotgun, and a Beretta 9 mm target pistol. He has only ever owned one car, a silver 1967 Chevrolet Camaro, which he has owned since he was 14.  Homme said that he "died" of asphyxiation for a short time in 2010, following unexpected complications during knee surgery. He contracted a MRSA infection, which his immune system could not fight due to stress. Doctors eventually used a defibrillator to revive him following the asphyxiation. The experience left him weakened and unable to produce music for almost two years. Following this, he was confined to his bed for three months and plunged into a deep depression, considering giving up his music career. He has said that this experience greatly contributed to the making of the Queens of the Stone Age album ...Like Clockwork. He credits Transcendental Meditation with helping him recover. In June 2016, he alluded that the story about his knee surgery may have been created by "somebody else", adding that he went "in too deep" involving drugs and sank into a depression.

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