The aim of this study was to evaluate the effect of different priming agents on the shear bond strength (SBS) of conventional and bioactive self-adhesive resin cements to zirconia. One hundred and twenty zirconia discs were randomly divided into four main groups according to the priming agents used (n = 30): no priming agent (control), zirconia primer (Z-PRIME Plus), universal adhesive (All-Bond Universal), and universal ceramic primer (Monobond N). Then, each group was subdivided into three subgroups according to the type of self-adhesive resin cement used: TheraCem, Activa BioActive, and RelyX U200 Automix (n = 10). All specimens were subjected to thermocycling. The mean SBS data were analyzed using One-Way ANOVA, followed by multiple comparison Bonferroni test. Without the application of priming agents (control), most of the specimens failed during thermocycling. The priming agent, cement type, and their interaction had a significant effect on the SBS to zirconia (p < 0.001). Only the type of priming agent showed a significant effect on the mode of failure (p < 0.001), resulting in mainly mixed failure with Monobond N and adhesive failure with other primers. Regardless of the type of primer, Bioactive resin cements did not improve the SBS to zirconia compared to conventional cements.