Noncentrosymmetric bulk materials effectively convert light energy into electricity by making use of the bulk photovoltaic effect (BPVE). However, whether such an effect persists when reducing the thickness of materials down to atomic-scale remains to be revealed. Here, we show the piezo-photovoltaic effect in atomically thin two-dimensional materials, where the strain-induced polarization can generate photovoltaic outputs in the noncentrosymmetric mono- and few-layer 2H-MoS2 crystals. The photocurrent is enhanced by orders of magnitude when the MoS2 crystals experience an in-plane strain of about 0.2%, with photopower-dependent responsivity up to 0.1 A/W that rivals other state-of-the-art BPVE materials. In addition, studies on the spatial distributions of photocurrents on MoS2 with a controlled number of layers also allow us to disentangle various factors that couple the piezoelectricity and photovoltaics. Therefore, our results also provide insights into the mechanisms of the piezo-photovoltaic effect in two-dimensional materials with thicknesses at the atomic-scale limit.