A simple and scalable technique is reported to demonstrate self-poled, flexible and superior-performance piezoelectric nanogenerators by using chemically exfoliated layered MoS2 nanosheets embedded in poly(vinylidene fluoride) (PVDF) polymers. These self-poled nanogenerators can produce an open-circuit voltage up to ∼22 V, even with an application of a very low mechanical compression (∼10.6 kPa) leading to an unprecedented piezoelectric output (2.07 V/kPa) using a two-dimensional material. On the other hand, in bending condition (∼0.11% strain), the nanogenerator device generates ∼2.5 V with a piezoelectric energy conversion efficiency of ∼17.8%, which is capable to drive multiple commercial light emitting devices. The fabricated flexible self-poled MoS2–PVDF nanogenerators have been used to harvest biomechanical energy from simple human activities (finger tapping, variation in movements of finger and wrist etc.) which offers an excellent power density of ∼88.5 μW/cm2 upon finger tapping (∼3.1 kPa) and displays a significant enhancement of performance over control PVDF devices. Our results open up the feasibility of using chemically exfoliated two-dimensional transition metal dichalcogenides for the design and development of high-efficiency, portable energy harvesting devices.