Ornithine δ-aminotransferase (δ-OAT) is a pyridoxal-5′-phosphate-dependent enzyme that has been proposed to be involved in proline (Pro) and arginine (Arg) metabolism. However, the actual role of δ-OAT in abiotic responses in plants remains to be clarified. Here we characterized an ornithine δ-aminotransferase gene OsOAT that confers multi-stress tolerance in rice (Oryza sativa). We confirmed that OsOAT is a direct target of the stress-responsive NAC transcription factor SNAC2. OsOAT is responsive to multiple stresses and phytohormone treatments. Both ABA-dependent and ABA-independent pathways contributed to the drought-induced expression of OsOAT. Overexpression of the OsOAT gene in rice resulted in significantly enhanced drought and osmotic stress tolerance. Overexpression of OsOAT caused significantly increased δ-OAT activity and Pro accumulation under normal growth conditions. In addition, OsOAT-overexpressing plants showed significantly increased tolerance to oxidative stress. The glutathione (GSH) content and activity of reactive oxygen species (ROS)-scavenging enzymes, such as glutathione peroxidase, were also increased in OsOAT-overexpressing plants. We conclude that OsOAT is a target gene of SNAC2 and confers stress tolerance mainly through enhancing ROS-scavenging capacity and Pro pre-accumulation.