Down-slope rock bridge in slopes and dangerous rock masses are often affected by cyclic wetting and drying, leading to severe geological disasters. In order to investigate the deterioration mechanism, deformation failure mode and instability precursor information of sandstone down-slope rock bridge under different cyclic wetting and drying, uniaxial compression tests combined with acoustic emission (AE) tests were conducted. The failure of the specimen experienced four stages. As the number of the cyclic wetting and drying increased, the specimen’s uniaxial compressive strength and elastic modulus decreased, and the failure mode transitioned from tensile to shear. Utilizing the critical slowing down theory, the variance and autocorrelation coefficient curves of AE multi-parameters were analyzed. The abrupt change of RA value, RA/AF value, and b value at the crack damage stress point and the abrupt change of the peak frequency lagging behind the crack damage stress point can be used as the precursors of instability. The instability precursor identified based on the peak frequency variance is closer to the specimen’s peak stress point and can be used for short-term failure prediction. The autocorrelation coefficient curve of AE multi-parameters aligned with the variance curve, indicating that with an increased number of cyclic wetting and drying, the instability precursor appeared earlier, leading to a larger failure prediction time interval.