Using desert sand (DS) to pour concrete is a feasible idea to solve the shortage of river sand. However, the frost resistance of desert sand concrete (DSC) is a key problem that must be solved for applying DSC in practical engineering. Therefore, this study on the performance and reliability analysis of DSC under a freeze–thaw cycle (FTC) was carried out. The DSC specimens were subjected to the FTC test with desert sand replacement ratios (DSRRs) of 0%, 20%, 40%, 60%, 80%, and 100%. Then, the appearance, mass, relative dynamic elastic modulus (RDEM), and compressive strength of DSC were analyzed and discussed. Moreover, the damage mechanism of DSC was discussed via microstructural analysis. The results indicated that as the FTCs increased, the mass loss rate of concrete increased, while the RDEM and compressive strength decreased. Among the samples, DSC-40 showed the best resistance to the FTC. After 250 cycles, the changes in mass, RDEM, and compressive strength of DSC-40 were 2.73%, 15.19%, and 27.2% lower than those of DSC0. Finally, the DSC reliability model was established by using the Weibull probability distribution method. Among all groups, DSC-40 showed the best reliability, and the failure life was 287 FTCs, which was approximately 1.55-times longer than DSC0. This model could provide a theoretical basis for the durability evaluation and life prediction of DSC structures in cold regions.