To study the variation laws and effects of asphalt mastic under the cooperative interaction of different temperatures and humidities, cyclic conditions for different temperature ranges were set to conduct indoor experimental simulations of thermal–humidity coupling cycles. Firstly, the macroscopic performance changes in styrene butadiene styrene polymer (SBS)-modified asphalt mastic were evaluated by the penetration test, softening point test, ductility test, Brookfield rotational viscosity test, and double-edge notched tensile (DENT) test; then, the mechanism of performance changes was explored from the perspective of chemical composition by combining this with Fourier transform infrared spectroscopy (FTIR). The research results show that with the increase in thermal–humidity coupling cycles, SBS-modified asphalt mastic exhibited aging phenomena such as hardening and embrittlement, and its macroscopic performance deteriorated; under the same test conditions, the interval with a higher temperature difference had a greater impact on the performance of the mastic; the sulfoxide index (I_S=O) of SBS-modified asphalt mastic increases after thermal–humidity coupling cycles, while the isoprene index (I_B) decreases.