The effects of sphere size on the microstructural and mechanical properties of ductile iron–steel hollow sphere (DI–SHS) syntactic foams were investigated in this study. The SHSs were manufactured by fluidized-bed coating via the Fe-based commercial powder–binder suspension onto expanded polystyrene spheres (EPSs). Afterwards, the DI–SHS syntactic foams were produced via a sand-mold casting process. The microstructures of specimens were investigated by optical microscopy, scanning electron microscopy (SEM), and energy- dispersive X-ray spectroscopy (EDS). The microscopic evaluations of specimens reveal distinct regions composed of the DI matrix, SHS shells, and compatible interface. As a result, the microstructures and graphite morphologies of the DI matrix depend on sphere size. When the sphere size decreases, the area fractions of cementite and graphite phases are observed to increase and decrease, respectively. Compression tests were subsequently conducted at ambient temperature on the DI–SHS syntactic foams. The results reveal that the compression behavior of the syntactic foams is enhanced with increasing sphere size. Furthermore, the compressed specimens demonstrate that microcracks start and grow from the interface region.