Grain refinement and enhanced mechanical properties of Mg–2Zn-xCa alloys (with a wide range of calcium contents from 0 to 5 wt%) were studied in both as-cast and extruded conditions. It was revealed that Ca addition can effectively refine the grain size of the ingots based on the growth restriction factor (GRF) mechanism, where at high Ca additions, the dendritic microstructure was obtained. By increasing the amount of Ca, the binary Mg–Zn phase was replaced by the Ca2Mg6Zn3 phase and at high Ca contents, the Mg2Ca phase appeared in the microstructure. The tensile properties were enhanced at low Ca additions (up to 0.3 wt%) due to the grain refinement but they were deteriorated at higher Ca additions due to the formation of grain boundary second phases. Accordingly, the ultimate tensile strength (UTS) of 228 MPa and total elongation of 20% was obtained for the as-cast Mg–2Zn-0.3Ca (ZX20) alloy. During hot extrusion, significant grain refinement and the fracturing and dispersion of second phase particles were observed. The grain size refinement beyond ~1 wt% Ca was negligible and extrusion defects were observed at higher Ca contents, and hence, the best combination of mechanical properties was obtained for the Mg–2Zn–1Ca (ZX21) alloy with UTS of 283 MPa and elongation to failure of 29%. This alloy showed a desirable work-hardening behavior and the best combination of tensile properties, where the product of tensile strength and total elongation reached as high as ~8000 MPa%. Finally, the yield stress of the alloys was correlated to the average grain size via the classical Hall-Petch plot with a slope of 228.5 MPa μm0.5.