Abiotic stresses such as water deficit, salt, and heat are major environmental factors that negatively affect plant growth, development, and productivity. Previous studies showed that overexpression of the Arabidopsis vacuolar H+-pyrophosphatase gene AVP1 increases salt and water deficit stress tolerance and overexpression of the rice SUMO E3 ligase gene OsSIZ1 improves heat and water deficit stress tolerance in transgenic plants. In this report, the effects of co-overexpression of AVP1 and OsSIZ1 in Arabidopsis on abiotic stress tolerance were studied. It was found that AVP1/OsSIZ1 co-overexpressing plants performed significantly better than AVP1-overexpressing plants and OsSIZ1-overexpressing plants, and produced 100% more seed than wild-type plants under single stress or multiple stress conditions. The increased stress tolerance in AVP1/OsSIZ1 co-overexpressing plants was substantially larger than the increased stress tolerance in AVP1-overexpressing plants and OsSIZ1-overexpressing plants under every abiotic stress condition tested. This research provides the proof-of-concept that crop yields might be substantially improved using this approach.