The first-principles plane-wave pseudopotential method is used to study the electronic and chemical structures of pyrite (FeS2) and arsenopyrite (FeAsS). The results indicate that an antibonding interaction occurs between Fe and As atoms in arsenopyrite. This interaction results in the Fe atom being repelled towards the S atom to stabilize antibonding orbitals, causing a larger S–Fe–S angle in arsenopyrite than in pyrite and a distortion in the arsenopyrite structure. In arsenopyrite, Fe–Fe distances are alternately long and short. The low spin density of the Fe d electrons supports this configuration in arsenopyrite. However, electron density calculations indicate that there is negligible electron density present between Fe atoms. This result indicates that cation-anion interactions are dominant in arsenopyrite. The pyrite Fe 3d orbital is split below the Fermi level, whereas the arsenopyrite Fe 3d orbital is not split, which can be attributed to the stronger interatomic bonding effects between Fe and S atoms in pyrite compared to arsenopyrite. It is found that the d-p orbital interactions between Fe and S atoms lead to bonding-antibonding splitting in both pyrite and arsenopyrite. However, the bonding effects between pyrite Fe and S atoms are stronger than in arsenopyrite. In arsenopyrite, the bonding interaction between the As 4p and Fe 3d orbitals is very weak, while the antibonding effect is very strong. The p-p orbital interaction is the dominant effect in As–S bonding. Frontier orbital calculations indicate that the Fermi levels of pyrite and arsenopyrite are notably close to each other, resulting in similar electrochemical activities. Orbital coefficient results show that the pyrite Fe 3d and S 3p orbitals are the active orbitals in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), respectively. In the case of arsenopyrite, Fe 3d orbitals are very active in both the HOMO and LUMO. Moreover, the activity of the As 4p in the HOMO is greater than S 3p, whereas the opposite situation occurs in the LUMO. Based on these results, As atoms could be one of the active sites for the oxidation of arsenopyrite. In addition, separation of arsenopyrite and pyrite could be achieved by utilizing the difference in chemical reactivities of iron in the two minerals.