Efficient formulations used in hydrometallurgy are often based on synergistic action of two oil-soluble extractants at an optimized mole fraction. In this series of two papers, we describe the N,N’-dimethyl-N,N’-dioctylhexylethoxymalonamide (DMDOHEMA)/di(2-ethylexyl) phosphoric acid (HDEHP) system, and how expression of the synergistic effect varies with acidity, using the three common representations: distribution ratios, yields, and free energies of transfer. The experimental results are detailed in this first part (Part I) with the so-called supramolecular approach, which considers the reverse micelle-like aggregates formed by the lipophilic extractant molecules. It shows that no specific aggregation state is observed at the maximum of synergism and antagonism. Besides, the critical aggregation concentration that characterizes the micellization free energy appears to follow some synergistic trends but cannot explain how acid tunes synergism to antagonism of this mixed system. Based on these results, Part II proposes a theoretical model based on the ienaic approach to interpret acid effect on synergism and antagonism.