The thermal history, and in particular the mixing dump temperature, is a parameter of paramount importance in mixing rubber and silica with a silane coupling agent in order to achieve proper silanization of silica and to avoid premature scorch reactions. The influence of the mixing dump temperature on the performance of silica-reinforced natural rubber (NR) is investigated. The investigation also includes the effect of nonrubber constituents, primarily proteins in NR, by using deproteinized natural rubber (DPNR) and synthetic polyisoprene (IR). The vulcanization properties and rubber-to-filler interactions of silica-reinforced NR in the presence and absence of a silane coupling agent are highlighted. With increasing mixing dump temperature, the silanization reaction between silica and silane coupling agent proceeds further. At a sufficiently high dump temperature, filler–filler interactions in the NR–silica compounds are reduced and the silica–rubber interaction improved, as evidenced by a drop in the Payne effect and increment in chemically bound rubber. It is demonstrated that NR and IR compounds mixed until they are above the optimum dump temperature exhibit cure reversion and reduction in tensile properties. On the other hand, DPNR–silica vulcanizates show slightly more constant physical properties.