Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH2Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5–7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH2Q increased with increasing pH and initial NH2Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ2−, has been shown to be the reactive species with regard to the one-electron oxidation by O2 and comproportionation with the quinone species, both generating the semiquinone radical (NSQ•−). The oxidation of NSQ•− by O2 is shown to be the most important pathway for superoxide (O2•−) generation with a high intrinsic rate constant of 1.0×108 M−1 s−1. Both NSQ•− and O2•− served as chain-propagating species in the autoxidation of NH2Q. Cu(II) is capable of catalyzing the oxidation of NH2Q in the presence of O2 with the oxidation also accelerated by increasing the pH. Both the uncharged (NH2Q0) and the mono-anionic (NHQ−) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×104 and 1.2×107 M−1 s−1, respectively. The presence of O2 facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ•− resulting in the generation of O2•−. The half-cell reduction potentials of various redox couples at neutral pH indicated good agreement between thermodynamic and kinetic considerations for various key reactions involved, further validating the proposed mechanisms involved in both the autoxidation and the copper-catalyzed oxidation of NH2Q in circumneutral pH solutions.