Jet-cooled acetaminophen (AAP)–water clusters, AAP–(H₂O)₁, were investigated by mass-selected resonant two-photon ionization (R2PI), ultraviolet–ultraviolet hole-burning (UV–UV HB), infrared-dip (IR-dip), and infrared–ultraviolet hole-burning (IR–UV HB) spectroscopy. Each syn- and anti-AAP rotamer has three distinctive binding sites (–OH, >CO, and >NH) for a water molecule, thus 6 different AAP–(H₂O)₁ conformers are expected to exist in the molecular beam. The origin bands of the AAP(OH)–(H₂O)₁ and AAP(CO)–(H₂O)₁ conformers (including their syn- and anti-conformers) in the R2PI spectrum are shifted to red and blue compared to those of the AAP monomer, respectively. These frequency shifts upon complexation between a water molecule and a specific binding site of AAP are also predicted by theoretical calculations. The spectral assignments of the origin bands in the R2PI spectra and the IR vibrational bands in the IR-dip spectra of the four lowest-energy conformers of AAP–(H₂O)₁, [syn- and anti-AAP(OH)–(H₂O)₁ and syn- and anti-AAP(CO)–(H₂O)₁], are aided by ab initio and time-dependent density functional theory (TDDFT) calculations. Further investigation of the IR-dip spectra has revealed a hydrogen-bonded NH stretching mode, supporting the presence of the syn-AAP(NH)–(H₂O)₁ conformer. Moreover, by employing IR–UV HB spectroscopy, we have reconfirmed the existence of the syn-AAP(NH)–(H₂O)₁ conformer, which happened to be buried underneath the broad background contributed by the AAP(OH)–(H₂O)₁ conformers. These observations have led us to conclude that all of the possible conformers of AAP–(H₂O)₁ have been found in this study.