Piezoelectric nanogenerators with large output, high sensitivity, and good flexibility have attracted extensive interest in wearable electronics and personal healthcare. In this paper, the authors propose a high-performance flexible piezoelectric nanogenerator based on piezoelectrically enhanced nanocomposite micropillar array of polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE))/barium titanate (BaTiO3) for energy harvesting and highly sensitive self-powered sensing. By a reliable and scalable nanoimprinting process, the piezoelectrically enhanced vertically aligned P(VDF-TrFE)/BaTiO3 nanocomposite micropillar arrays are fabricated. The piezoelectric device exhibits enhanced voltage of 13.2 V and a current density of 0.33 µA cm−2, which an enhancement by a factor of 7.3 relatives to the pristine P(VDF-TrFE) bulk film. The mechanisms of high performance are mainly attributed to the enhanced piezoelectricity of the P(VDF-TrFE)/BaTiO3 nanocomposite materials and the improved mechanical flexibility of the micropillar array. Under mechanical impact, stable electricity is stably generated from the nanogenerator and used to drive various electronic devices to work continuously, implying its significance in the field of consumer electronic devices. Furthermore, it can be applied as self-powered flexible sensor work in a noncontact mode for detecting air pressure and wearable sensors for detecting some human vital signs including different modes of breath and heartbeat pulse, which shows its potential applications in flexible electronics and medical sciences.