Organisms have developed different strategies to cope with environmental conditions of low Fe availability based on the exudation of reducing, ligating, and acidifying compounds. In the context of Fe acquisition from soil, the effects of these reactive compounds have generally been considered independent and additive. However, highly efficient Fe acquisition strategies may rely on synergistic effects between reactive exudates. In the present study, we demonstrate that synergistic effects between biogenic ligands and a reductant (ascorbate) can occur in Fe mobilization from soil. Synergistic Fe mobilization was found for all ligands examined (desferrioxamine B (DFOB), 2'-deoxymugineic acid (DMA), esculetin, and citrate). The size and duration of the synergistic effect on Fe mobilization varied with ligand: larger effects were observed for the sideorphores compared to esculetin and citrate. For DFOB, the synergistic effect lasted for the 168 h duration of the experiment; for DMA, an initial synergistic effect turned into an antagonistic effect after 4 h because of enhanced mobilization of competing metals; and for esculetin and citrate, the synergistic effect was temporary (less than 24 h). Our results demonstrate that synergistic effects greatly enhance the reactivity of mixtures of compounds known to be exuded in response to Fe limitation. These synergistic effects could be decisive for the survival of plants and microorganisms under conditions of low Fe availability.