Grenier was born in Santa Fe, New Mexico and raised in Manhattan, New York, by his mother, Karesse Grenier, a real estate agent. His mother met his father, John Dunbar, in a commune in the 1970s and the two were never married. Grenier is of Apache and European descent. He went to Bard College in New York.
In 1997, Grenier made his film debut in the independent drama Arresting Gena. In 1999, he played opposite Melissa Joan Hart in Drive Me Crazy as well as in Britney Spears' music video "Crazy", and in 2001, starred in James Toback's Harvard Man. In 2002, Grenier made his directorial debut with the documentary, Shot in the Dark. The documentary chronicles his years-long search for his father, with whom Grenier's mother broke up when Adrian was still a baby. Grenier and Dunbar remained estranged for 18 years, and in 2001, Adrian began work on the documentary in an attempt to forge a relationship with Dunbar. The two eventually reunited and maintain a warm relationship. HBO premiered the documentary on June 3, 2007.
In 2004, Grenier landed the lead role in the HBO series Entourage, which has brought him his most substantial notice and success. In 2006, he won a role in The Devil Wears Prada, as Anne Hathaway's boyfriend, Nate.
On June 2, 2008, Grenier's new show, Alter Eco, premiered on Planet Green. The show features the actor and his team of green experts showing changes that can be made to become more eco-friendly.
On September 27, 2010 HBO premiered the documentary Teenage Paparazzo, a film concerning the relationship between the celebrity and society that Grenier worked on for three years as a producer. The work features interviews with celebrities such as Lindsay Lohan, Alec Baldwin, and Whoopi Goldberg.
