Area-selective atomic layer deposition (ALD) of lead sulfide (PbS) was achieved on octadecyltrichlorosilane (ODTS)-patterned silicon substrates. We investigated the capability of ODTS self-assembled monolayers (SAMs) to deactivate the ALD PbS surface reactions as a function of dipping time in ODTS solution. The reaction mechanism was investigated using density functional theory (DFT), which showed that the initial ALD half-reaction is energetically unfavorable on a methyl-terminated SAM surface. Conventional photolithography was used to create oxide patterns on which ODTS SAMs were selectively grown. Consequently, PbS thin films were grown selectively only where ODTS was not present, whereas deposition was blocked in regions where ODTS was grown. The resulting fabricated patterns were characterized by scanning electron microscopy and Auger electron spectroscopy, which demonstrated that ALD PbS was well confined to defined patterns with high selectivity by ODTS SAMs. In addition, AFM lithography was employed to create nanoscale PbS patterns. Our results show that this method can be applied to various device-fabrication processes, presenting new opportunities for various nanofabrication schemes and manifesting the benefits of self-assembly.