Two different microstructures of an Al-12Si (wt. %) alloy were produced, respectively, via a powder laser bed fusion (P-LBF) additive manufacturing and casting. Compared to casting, additive manufacturing of Al-based alloy requires extra care to minimize oxidation tendency. The role of the microstructure on the mechanical properties of Al-12Si (wt. %) alloy was investigated by in situ compression of the micro-pillars. The microstructure of additively manufactured specimens exhibited a sub-cellular (~700 nm) nature in the presence of melt-pool arrangements and grain boundaries. On the other hand, the microstructure of the cast alloy contains typical needle-like eutectic structures. This striking difference in microstructure had obvious effects on the plastic flow of the materials under compression. The yield and ultimate compressive strength of the additively manufactured alloy were 23.69–27.94 MPa and 75.43–81.21 MPa, respectively. The cast alloy exhibited similar yield strength (31.46 MPa); however, its ultimate compressive strength (34.95 MPa) was only half that of the additively manufactured alloy. The deformation mechanism, as unrevealed by SEM investigation on the surface as well as on the cross-section of the distorted micro-pillars, confirms the presence of ductile and quasi-ductile facture of the matrix and the Si needle, respectively, in the case of the cast alloy. In contrast, the additively manufactured alloy exhibits predominantly ductile fractures.