Quinones have a capacity for high energy storage and exhibit facile and reversible electrochemistry in several widely different electrolytes. They are, therefore, one of the most popular compounds currently used in organic materials based electrical energy storage. Quinone electrochemistry is, however, strongly affected by the composition of the electrolyte. This report summarizes our systematic investigation of the redox chemistry of a series of quinones with electron-withdrawing and electron-donating substituents in aqueous solution and in acetonitrile (MeCN) with tetrabutylammonium (TBA+)-, Li+-, and H+-based electrolytes. As a general trend, proton cycling, TBA+ cycling, and Li+ cycling resulted in the highest, the lowest, and intermediate redox potentials, respectively. We attribute this trend to stabilization of the reduced state, namely benzene-1,4-bis(olate) (Q2-), by the different counterions. Density functional theory (DFT) calculations showed that, in the fully reduced state, two Li+ counterions accommodated 35% of the injected electron charges while proton counterions accommodated 69% of the injected charge, thus significantly stabilizing the reduced state. However, with the bulky TBA+ as the cycling ion, this stabilization was not possible and the reduction potential was decreased. In addition, we showed that stabilization of the counterion also affected the Coulombic interaction between the successively injected charges, resulting in the well-known disproportionation of the semiquinone radical intermediate state with proton cycling, while Li+ and TBA+ cycling generally resulted in two consecutive redox reactions. Finally, we showed that the electrolyte strongly influences the effects of substitution with electron-donating and electron-withdrawing substituents. A strong relationship between the redox potential and the electron-withdrawing power of the substituent was observed in the MeCN solution. However, this relationship was completely lost in aqueous solution. The reason for the loss of the relationship was addressed using a DFT explicit-solvent model and is discussed. © 2020 American Chemical Society.