Copper (Cu)-based catalysts generally exhibit high selectivity toward valuable C2+ products during the electrochemical CO2 reduction reaction (CO2RR). However, the origin of this selectivity and the influence of precursor materials on it are not fully understood due to the elusive evolution of catalysts during the CO2RR. We combined operando X-ray diffraction (XRD) and operando Raman spectroscopy to monitor the structural and compositional evolution of three oxidized Cu precursors (Cu2(OH)2CO3, Cu(OH)2, and CuO) during the CO2RR. The results indicated that the three precursors were completely reduced to Cu(0) with similar grain sizes (~ 11 nm) despite their different electroreduction kinetics when delivering their maximum Faradaic efficiencies for C2+ products. The high density of grain boundaries associated with the small grain size explains their significantly enhanced C2+ selectivity (68–73%) compared to bulk Cu (~ 13%). Operando Raman spectroscopy revealed the lack of co-occurrence of CO2RR intermediates and Cu2(OH)2CO3, Cu(OH)2, CuO, or Cu2O, ruling out the involvement of these oxidized Cu species in the CO2RR. Most interestingly, operando XRD indicated that the Cu nanocrystals derived from Cu(OH)2 and Cu2(OH)2CO3 exhibited noticeable tensile strains of 0.43%~0.55% during the in situ electroreduction of precursors, which could not be detected by conventional ex situ XRD. In contrast, Cu nanocrystals derived from CuO were hardly strained. Density functional theory calculations suggested that the tensile strain in Cu lattice is conducive to promoting the overall CO2RR selectivity, which is consistent with the experimental observations. Therefore, the excellent CO2RR performance of some derived Cu catalysts is attributed to the combined effect of the small grain size and lattice strain, both of which are the result of the in situ electroreduction of precursors. The findings, for the first time, establish correlations between Cu precursors, lattice strains, and catalytic behaviors, demonstrating the unique ability of operando characterization techniques in probing catalyst evolution during electrochemical processes.