Purpose: To compare the bond strengths of three types of permanent silicone and acrylic resin soft liners to the denture-base acrylic resin by employing both synchronous and asynchronous processing methods and different surface treatments. Materials and Methods: A total of 198 cylindrical samples were fabricated from denture-base acrylic resin and a 3-mm soft liner. Surface treatments of the samples were classified into five groups (n = 33 each): no treatment (control); erbium:yttrium-aluminum-garnet (Er:YAG) laser; grit-blasting with 150-μm particles; monomer application; and phosphoric acid application. In addition, synchronous processing (n = 33) of the acrylic resin denture base and the soft liner was performed. Each group was divided into three subgroups (n = 11 each) based on the type of soft liner: Group M (Molloplast-B [silicone]), Group P (PermaFlex [silicone]), and Group A (AcroSoft [acrylic resin]). The samples were processed and thermocycled for 5,000 cycles between 5°C and 55°C, and the tensile strength test was then performed. The maximum tensile strength to failure and the type of failure were recorded, and Dunn statistical analysis and Kruskal-Wallis tests were used for comparison of the groups. The surface treatments were assessed using scanning electron microscopy. Results: Irrespective of the method of processing or surface treatment, Group A had a significantly higher bond strength (8.1 ± 1.1 MPa) than the other two soft liners (Group M: 1.9 ± 0.3 MPa, Group P: 1.1 ± 0.2 MPa; P .001). Moreover, in Group A, the synchronous processing method produced a significantly higher tensile strength (P .001), while in Group P (P = .112) and Group M (P = .993), synchronous processing had no significant effect on bond strength. Bond strength after surface treatment in Group M was lowest after grit blasting (0.7 ± 0.2 MPa) and highest after monomer application (3.1 ± 0.5 MPa) (P .001). The same was observed for Group P in grit blasting (0.5 ± 0.2 MPa) and monomer application (2.1 ± 0.3 MPa) (P .001). For Group A, grit blasting (4.8 ± 0.7 MPa) was also the lowest and the monomer application (8.1 ± 0.8 MPa) the highest (P .001), while the bond strength resulting from the synchronous processing method was higher than that of the other methods (14.7 ± 2.1 MPa). Conclusion: Within the limitations of this in vitro study, the acrylic resin soft liner showed the best bond strength. In all types of soft liners, surface treatment with the monomer resulted in higher bond strengths. Synchronous processing exhibited a significantly higher bond strength for the acrylic resin soft liner, but not for the silicone soft liners.