Background: This in vitro study aimed to investigate and evaluate the values of water sorption and water solubility of four types of denture base polymers—3D-printed NextDent 3D Denture + (NextDent, 3D Systems, Soesterberg, The Netherlands), CAD/CAM milled Ivotion Base (Ivotion Denture System, Ivoclar Vivadent, Schaan, Liechtenstein), PMMA conventional Vertex BasiQ 20 (Vertex Dental, 3D Systems, Soesterberg, The Netherlands), and conventional heat-cured BMS (BMS Dental Srl, Rome, Italy)—which were subjected to artificial aging. Materials and methods: 200 specimens were created (n = 50), dried, and weighed accurately. They were immersed in artificial saliva (T1 = 7 days, T2 = 14 days, T3 = 1 month) and re-weighed after water absorption. After desiccation at 37 °C for 24 h and then at 23 ± 1 °C for 1 h, samples were weighed again. Next, thermocycling (100 h, 5000 cycles, 5–55 °C) was performed, and the water sorption and solubility were re-measured. IBM SPSS Statistics 0.26 was used for data analysis, revealing a direct correlation between water sorption and material type. Thermocycling at 55 °C increased water sorption for BMS and Vertex BasiQ 20. In conclusion, NextDent’s 3D-printed resin had higher water sorption values throughout the study. Water solubility averages decreased over time, reaching the lowest in the 30-day period for CAD/CAM milled dental resin Ivotion Base. The artificial aging had no effect on Ivotion Base and NextDent’s water sorption. Thermocycling did not affect the solubility of the materials tested. The conducted study acknowledges the great possibilities of dental resins for additive and subtractive manufacturing for the purposes of removable prosthetics in daily dental practice.