Electrochemical reduction (ECR) and oxidation (ECO) of 5,6,7,8-tetrafluoroquinoxaline (1) and its derivatives bearing various substituents R (7-H (2), 7,8-H2 (3), 6-CF3 (4), 6-Cl (5), 5,7-Cl2 (6), 5-NH2 (7), 6-OCH3 (8), 6,7-(OCH3)2 (9), 6,7,8-(OCH3)3 (10), 5,6,7,8-(OCH3)4 (11), 6-OCH3,7-N(CH3)2 (12), 6-N(CH3)2 (13), 6,7-(N(CH3)2)2 (14), 5,6,7-(N(CH3)2)3 (15), and 7,8-cyclo-(=CF-CF = CF-CF=) (16)) in the carbocycle have been studied by cyclic voltammetry in MeCN. For 1–4 and 7–15, the first reduction peaks have been found to be 1-electron and reversible, thus corresponding to the formation of their radical anions (RAs), which are long lived at 295 K except those of 4–6 and 15, 16. Irreversible hydrodechlorination has been observed for 5 and 6 at the first step of their ECR confirmed by EPR detection of corresponding RAs of 2 and 5,7-H2 derivative of 1 (17) at the next steps. Electrochemically generated RAs of 1–3, 7–14, and 17 have been characterized in MeCN by EPR spectroscopy together with DFT calculations at the (U)B3LYP/6-31 + G(d) level of theory using PCM to describe the solvent. A noticeable alternation of spin density on the –NCCN– moiety of quinoxaline has been observed for all RAs possessing R-substitution asymmetry. The comparative electron-accepting ability of 1–15 has been analyzed in terms of their experimental reduction peak potentials and the (U)B3LYP/6-31 + G(d)-calculated gas-phase first adiabatic electron affinities (EAs). The differences in electron transfer solvation energies for 1–15 have been evaluated on the basis of ECR peaks' potentials and calculated gas-phase EAs. The ECO of 1–5 and 7–14 has been found to be irreversible.