High-performance gas sensors based on metal oxides operated at room temperature are of great interest due to their energy saving and cost effective characteristics. How to improve the sensitivity of metal oxide gas sensors and enable their room-temperature operation are challenging for their realistic applications. In this work, we have designed and fabricated Al-doped NiO nanosheets for greatly enhanced NO2 detection at room temperature. Different amounts of Al were doped into two-dimensional (2D) NiO nanosheets via a fast and facile microwave assisted solvent-thermal technique. Sensing tests of the as-fabricated devices indicated that Al doping could significantly affect the gas-sensing properties of the NiO nanosheets due to increased oxygen vacancies as well as the formation of Lewis acid and base sites. When 12 at% of Al was added to the raw materials, the response value of the device to 10 ppm NO2 was enhanced more than 35 times compared with those of pure NiO nanosheets. In addition, when the amount of Al reached 20 at%, it took only 200 s for the gas sensor to achieve full recovery, which was a breakthrough for room temperature gas sensors based on metal oxides. Above all, the excellent performances of the as-fabricated devices make Al-doped NiO nanosheets a potential candidate for NO2 sensing applications. This design strategy can also give guidance for designing high-performance gas sensors based on other similar 2D sensing materials.