This study explores the performance of asphalt mixtures modified with North American rock asphalt and desulfurized rubber particles at varying rubber-to-asphalt ratios ranging from 18% to 36% by weight. A comprehensive set of laboratory tests, including high-temperature rutting tests, low-temperature bending tests, indirect tensile tests, and freeze–thaw splitting tests, were conducted to evaluate the modified mixtures. The results indicate that both wet and dry blending methods produce mixtures that meet technical requirements, with the optimal asphalt-to-aggregate ratio determined to be 7.1%. At a rubber-to-asphalt ratio of 18%, the wet blending method slightly improves high-temperature rutting resistance compared to the dry method. However, an increase in rubber content generally enhances rutting resistance regardless of the blending technique. The wet blending method excels in low-temperature crack resistance, possibly due to better rubber dispersion, while an increase in rubber content diminishes crack resistance due to a thinning asphalt film. In terms of fatigue performance, the dry blending method results in significantly longer fatigue life, with a 27% rubber-to-asphalt ratio exhibiting optimal balance. The dry method consistently outperforms the wet method in water stability, and the resistance to water damage increases with rubber content. In conclusion, this study provides valuable insights into optimizing rubber-to-asphalt ratios and blending methods for various application needs, showcasing the benefits of rock asphalt and desulfurized rubber particles in asphalt modification.