The main purpose of this research is to assess the influence of different design parameters on the mechanical performance of high-performance fiber-reinforced concrete (HPFRC) mixtures. Special attention is also paid to achieving deflection-hardening behavior in the presence of a large amount of coarse aggregates. Different mixture design parameters were the initial curing ages (3, 7, 28, and 90 days), ratios of Class F fly ash (FA) to portland cement (PC) (0.0, 0.2, and 0.4), addition/type of nanomaterials [nanosilica (NS), nanoalumina (NA), and nanocalcite (NC)], and combinations of fibers [polyvinyl-alcohol + steel (P, S) or brass-coated microsteel + steel (B, S)]. The experimental program included the evaluation of compressive strength, flexural strength, and midspan deflection results in addition to test parameters recorded under biaxial flexural loading via a series of square panel tests, including peak load and energy absorption capacities. Test results revealed that deflection-hardening response coupled with multiple microcracks can be obtained when large amounts of coarse aggregates are available for all HPFRC mixtures. As expected, experimental results change depending on the different curing ages and FA/PC ratios. The most distinctive parameters affecting the results are addition/type of nanomaterials and the presence of different fiber combinations. In the presence of nanomaterials, all results from the different tests improved, especially for NA and NS inclusions. With slight concessions in flexural deflection results, B fiber is shown to be a successful candidate to fully replace costly P fibers because most properties of B, S fiber-reinforced HPFRC mixtures outperformed those with P, S fibers, both under four-point bending and biaxial flexural loading.