•A novel sub-ppm NO2 gas sensor based on a few-layered mesoporous graphene (FLMG).•Few-layered mesoporous graphene is optimized at 100 min by a high-energy ball milling.•The room-temperature sensor exhibited high sensitivity, low cost and simple fabrication.•FLMG-based sensor shows an insignificant NH3 and humidity interference. Few-layered mesoporous graphene (FLMG) is employed as a sensing material to develop an innovative and high-sensitivity room temperature NO2 sensor through a simple manufacturing process. For this purpose, sensing material is optimized at 100 min by a high-energy milling process where natural graphite is used as a precursor: it is an inexpensive, sustainable and suitable active material. The large number of defects created and the enhanced degree of mesoporosity produced during the milling process determine the physical principles of operation of the designed device. NO2 gas sensing tests reveal an improved and selective performance with a change in resistance of ∼16 % at 0.5 ppm under ultraviolet photo-activation, establishing a detection limit around ∼25 ppb. Interestingly, the response of the developed sensor to humidity is independent in the measured range (0–33 % relative humidity at 25 °C) and the dependency to the presence of NH3 is rather poor as well (∼1.5 % at 50 ppm).