Purpose The aim of this study was to inspect the mechanical fatigue behavior of an implant-supported restorative system using polyether ether ketone (PEEK) and yttria partially stabilized zirconia polycrystals (YZ) as materials for customized definitive implant-supported hybrid abutments, supporting two types of all-ceramic restorations: translucent zirconia (TZ) and lithium disilicate (LD) monolithic crowns. Materials and methods Forty Morse taper implants were included in epoxy resin. Titanium intermediary abutments were placed, and the specimens were randomly allocated into four groups (n = 10) according to the customized hybrid abutment material (PEEK or YZ) and the monolithic crowns (TZ or LD) representing a maxillary central incisor crown. The specimens were subjected to a mechanical fatigue test (step-stress analysis) by means of an initial 200-N load for 5,000 cycles and subsequent increase of 50 N (step-size) at each 10,000 cycles, until failure occurred. The load at failure and number of cycles until failure were recorded; survival probabilities and specimen displacement were calculated for each step. The failure pattern was evaluated, and the Weibull modulus was obtained for each condition. Results Fatigue of both types of crowns was not influenced by the abutment material (LD-PEEK = LD-YZ; TZ-PEEK = TZ-YZ). In the PEEK abutment, the values obtained in the LD and TZ crowns showed no statistical difference; however, in the YZ abutment, the TZ crown presented a load at failure value that was statistically higher than that for LD. Failure pattern analysis revealed a higher prevalence of crown fracture for LD groups, while screw/implant platform fractures were shown for TZ groups. Conclusion YZ and PEEK hybrid abutments promoted similar fatigue levels regardless of the crown materials, TZ crowns promoted a higher fatigue level than LD ones when associated with YZ abutments, and LD crowns promoted a similar fatigue level to TZ ones when associated with PEEK custom abutments. Higher prevalence of crown fractures was shown for LD and screw/implant platform fractures for TZ groups.