This study investigates the preparation and performance of ultra-high-performance concrete (UHPC) incorporating manufactured sand as a full replacement for quartz sand. The mix design was optimized by integrating the compressible packing model (CPM) with an orthogonal experimental design. The influence of stone powder content in manufactured sand—0, 5, 10, and 15% by mass of fine aggregate—on fresh-state fluidity and 7d-mechanical properties was systematically evaluated. Hydration products and microstructural features were analyzed using X-ray diffraction (XRD), scanning electron microscope (SEM), and mercury intrusion porosimetry (MIP). Results show that the manufactured sand-based UHPC achieved a fresh-state fluidity of 185 mm and a 7-day compressive strength of 152.4 MPa. Both fluidity and compressive strength exhibited a unimodal trend with increasing stone powder content, reaching maxima at 10%. Microstructural analysis revealed intimate interfacial bonding between unhydrated particles and calcium silicate hydrate (C–S–H) gel; notably, the UHPC matrix with 10% stone powder displayed the densest microstructure. MIP results further demonstrated that an optimal stone powder content effectively reduced total porosity, with the lowest overall porosity and the highest volume fractions of harmless (≤20 nm) and less harmful (20–100 nm) pores observed at 10%. These microstructural refinements collectively underpin the superior mechanical performance of manufactured sand-based UHPC.