Metal-halide perovskites are promising optical gain materials because of their excellent photophysical properties. Recently, large perovskite single crystals with phase purity, less defects, and over millimeter dimensions have been successfully synthesized. However, the optical gain effect from these large-size single crystals has not yet been realized. Herein, we for the first time report efficient two-photon pumped amplified spontaneous emission (ASE) from millimeter-sized CsPbBr3 single crystals (SCs) with a low threshold of 0.65 mJ cm-2 and an optical gain of 38 cm-1. Furthermore, the CsPbBr3 SCs also exhibit ultrastable ASE under continuous laser irradiation for more than 40 h (corresponds to 1.5 × 108 laser shots) at ambient condition. This work suggests the potential application of large-size perovskite single crystals in practical nonlinear optical devices.