Acidic soils are characterized by the co-occurrence of phytotoxic concentrations of aluminum (Al3+) and iron (Fe2+/Fe3+); however, the interactive effects of these elements within plants and the root environment remain poorly understood. In this study, Amaranthus retroflexus, an Al-accumulating species, was grown hydroponically at pH 4.0 in Al-free (–Al) control or treated with two levels of Al (50 µM, and 400 µM), in combination with either no Fe (–Fe), adequate Fe (20 µM Fe), or excess Fe (100 µM Fe). Leaf chlorosis was induced by Al in Fe-sufficient plants and intensified under Fe deficiency, coinciding with elevated ferric chelate reductase (FRO) activity in roots while Al reduced FRO activity under excess Fe supply. The leaf contents of phenolics and betacyanin increased with rising Al and Fe levels, peaking under the combined application of high Al and excess Fe. Both Fe deficiency and Fe toxicity stimulated the exudation of phenolics and organic acids. Citrate was the predominant carboxylate exuded by Al-free plants, whereas oxalate became dominant under high Al exposure. Aluminum and Fe treatments both reduced foliar accumulation of the other element, with indirect evidence suggesting that Al limits Fe mobility and bioavailability in leaf tissues. These findings demonstrate that A. retroflexus activates internal and external detoxification mechanisms in response to combined Al and Fe toxicity, highlighting a coordinated adaptive strategy for survival in acid soil environments.