This study investigates the synergistic effect quarry dust, as a partial replacement for fine aggregate, and micro-silica, used as a partial replacement for cement, on the compressive and flexural strength of high-strength concrete (HSC), with a target grade of 80 MPa. Twenty mixes were produced using a combined percentage replacement of 0%, 5%, 10%, 15%, and 20%, across four water-binder ratios of 0.20, 0.24, 0.28, and 0.32. Compressive strength was measured at curing ages of 3, 7, 14, and 28 days, while flexural strength (modulus of rupture) was determined experimentally on prisms at 28 days and further compared against values predicted by the Eurocode 2 and ACI 318-11 code equations. Results showed that strength increased with percentage replacement up to an optimum of 10% PR, beyond which it declined, with the highest 28-day compressive strength of 73.40 MPa and highest flexural strength of 5.85 MPa both recorded at 10% PR and a water-binder ratio of 0.20, representing increases of 27.43% and 16.30% respectively over the control mixture. The Eurocode 2 equation consistently overestimated experimental flexural strength by approximately 10%, while ACI 318-11 underestimated it by approximately 17–18%. Result also revealed that combined 10% quarry dust and micro-silica replacement at a water-binder ratio of 0.20 produced the maximum strength performance and is recommended for high-end structural applications.