As a promising material for photoelectrical application, MoS2 has attracted extensive attention on its facile synthesis and unique properties. Herein, we explored a novel strategy of laser ablation to synthesize MoS2 fullerene-like nanoparticles (FL-NPs) with stable photoresponse under high temperature. Specifically, we employed a millisecond pulsed laser to ablate the molybdenum target in dimethyl trisulfide gas, and as a result, the molybdenum nanodroplets were ejected from the target and interacted with the highly reactive ambient gas to produce MoS2 FL-NPs. In contrast, the laser ablation in liquid could only produce core-shell nanoparticles. The crucial factors for controlling final nanostructures were found to be laser intensity, cooling rate, and gas reactivity. Finally, the MoS2 FL-NPs were assembled into a simple photoresponse device which exhibited excellent thermal stability, indicating their great potentialities for high-temperature photoelectrical applications.