Arsenic is a widespread environmental toxin having devastating impacts on human health. A transition to anaerobic conditions is a key driver for promoting As desorption through either the reduction of As(V) or the reductive dissolution of Fe(III) (hydr)oxides. However, a disparity in the reported release sequence for As and Fe to the aqueous solution hinders our ability to determine the controlling factors liberating As to the aqueous environment. Accordingly, we performed a thermodynamic analysis of Fe, using a range of Fe-(hydr)oxides, and As reduction coupled with hydrogen, acetate, and lactate oxidation for a range of relevant field conditions. The favorability of sulfate reduction is also evaluated. Our results illustrate that As reduction is favorable over a wide-range of field conditions, and Fe reduction is differentially favorable depending on the buildup of metabolites (mainly Fe2+) and the Fe (hydr)oxide being reduced; reduction of As(V) is thermodynamically favorable under most environmental conditions and almost always more favorable than goethite and hematite reduction. Sulfate reduction is favorable over a range of conditions, and may occur concomitantly with Fe reduction depending on the Fe (hydr)oxides present. Thus, on a thermodynamic basis, the general sequence of microbial reduction should be As(V) followed by Fe(III) or sulfate.