1. To go or act outside the bounds of control, propriety, or acceptance of a given group. The phrase refers to the forced relocation of Native Americans to Indian reservations in the United States. Because of this origin, the phrase is often considered offensive or inappropriate. The youths in this area are going off the reservation more and more these days, disregarding anything they see as a form of authority.

2. To think or act differently or contrary to the accepted norm. The vice president seems to have gone off the reservation regarding his views on legalizing marijuana.