Soil microorganisms are indispensable for a healthy soil environment, where the fate of pesticides is contingent on microbial activity. Conversely, soil ecosystems can be distorted by all kinds of variables, such as agrochemicals. These crop protection products have been universally in use for decades in agriculture. In modern crop cultivation, fungicides are increasingly applied because of their high and broad effectivity on plant pathogens. While their use can enhance harvest yields, fungicides, particularly broad-spectrum ones, are responsible for the alteration of the soil microflora. Furthermore, successive and combined application of pesticides is an agronomic routine, which aggravates the concurrent existence of synthetic chemicals in the soil and marine environments. Mutual interactions of such different molecules, or their effects on soil life, can negatively impact the dissipation of biodegradable pesticides from the ecosystems. The direct effects of individual agrochemicals on microbial soil parameters, as well as agronomic efficiency and interactions of mixtures have been thoroughly studied over the past 80 years. The indirect impacts of mixtures on soil and aquatic ecosystems, however, may be overlooked. Moreover, the current regulatory risk assessment of agrochemicals is based on fate investigations of individual substances to derive predicted environmental concentrations, which does not reflect real agricultural scenarios and needs to be updated. In this article, we summarized the results from our own experiments and previous studies, demonstrating that the degradation of pesticides is impacted by the co-existence of fungicides by their effects on microbial and enzymatic activities in soil.