The present work encompasses the effect of Li+ ions on CaO nanoparticles for the transesterification of lard oil. The modification of CaO nanoparticles was achieved by the impregnation of different molar ratios of lithium hydroxide. Later, each catalyst was screened for the catalytic conversion of lard oil to a fatty acid methyl ester (FAME). The nanocatalyst CaO–0.5LiOH (1 : 0.5 molar ratio) showed the best conversion rate for FAME. The synthesized nanocatalyst was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) analysis, and Hammett indicators for the basicity test. The obtained FAME was analyzed by gas chromatography with mass spectrometry (GC-MS) and 1H and 13C nuclear magnetic resonance (NMR). The effect of optimum reaction parameters such as catalyst weight percentage, oil-to-methanol ratio, reaction time, reaction temperature, and reusability of the catalyst for the transesterification reaction was analyzed by 1H NMR. The maximum FAME yield of 97.33% was obtained with 4 wt% catalyst amount and 1 : 6 oil-to-methanol ratio at 65 °C in 120 minutes. The physical properties of the synthesized FAME were also determined.