This article examines the effects of thermal aging and chemical disinfection on the microhardness and flexural strength of flexible resins. The influence of the resin type on the mechanical properties was also investigated. Two flexible resins, Deflex Classic SR and Deflex Supra SF, produced by the injection method, and a thermopolymerizable acrylic resin—ProBase Hot, produced by the flasking method, were subjected to 1000 cycles of thermal aging and three chemical disinfection protocols (n = 8), with daily immersion and during a recommended time, in Corega Whitening, Corega Oxygen Bio-Active, 2.5% sodium hypochlorite, and distilled water (control). Knoop microhardness and three-point flexural strength were evaluated. Data were analyzed using Wilcoxon, Mann–Whitney and Kruskal Wallis tests (α = 0.05). The results varied between 14.5 KHN and 80.1 MPa for ProBase Hot and 7.3 KHN for Deflex Classic SR and 52.5 MPa for Deflex Supra SF. Thermal aging reduced the microhardness of the flexible resins, but not their flexural strength. The microhardness of Deflex Classic SR was influenced by chemical disinfection with Corega Bio-active (p < 0.001). The flexural strength of Deflex Supra SF was influenced by chemical disinfection with Corega Whitening (p < 0.05). It can be concluded that chemical disinfection led to changes in the flexible resins and should be used with caution to maintain the mechanical properties of the resins. Flexible resins showed reduced resistance to physical and chemical environmental influences, which can affect their longevity.