Area-selective atomic layer deposition (AS-ALD) is a highly sought-after strategy for the fabrication of next-generation electronics. This work reveals how key precursor design parameters strongly influence the efficacy of AS-ALD by comparing a series of precursors possessing the same metal center but different ligands. When the number of methyl and chloride groups in Al(CH₃)_xCl_3–x (x = 0, 2, and 3) and the chain length of alkyl ligands in AlC_yH_2y+1 (y = 1 and 2) are changed, the effect of precursor chemistry (reactivity and molecular size) on the selectivity is elucidated. The results show that optimized parameters for the Al₂O₃ ALD processes on a self-assembled monolayer (SAM)-terminated substrate, which serves as the nongrowth surface, differ significantly from those on a Si substrate. Chlorine-containing precursors need a much longer purging time on the SAMs because of a stronger Lewis acidity compared to that of alkyl precursors. With reoptimized conditions, the ALD of Al₂O₃ using the Al(C₂H₅)₃ precursor is blocked most effectively by SAM inhibitors, whereas the widely employed Al(CH₃)₃ precursor is blocked least effectively among the precursors tested. Finally, we show that a selectivity exceeding 0.98 is achieved for up to 75 ALD cycles with Al(C₂H₅)₃, for which 6 nm of Al₂O₃ film grows selectively on SiO₂-covered Si. Quantum chemical calculations show significant differences in the energetics of dimer formation across the Al precursors, with only ∼1% of AlCl₃ and Al(CH₃)₂Cl precursors but 99% of the alkyl precursors, Al(CH₃)₃ and Al(C₂H₅)₃, existing as monomers at 200 °C. We propose that a combination of precursor reactivity and effective molecular size affects the blocking of the different precursors, explaining why Al(C₂H₅)₃, with weaker Lewis acidity and relatively large size, exhibits the best blocking results.