Dissecting the connection between drought stress and aflatoxin contamination in maize and peanut has led to the observation that drought tolerant, aflatoxin contamination-resistant plants tend to accumulate less reactive oxygen species (ROS) in their tissues under stress conditions. Oxidative stress also leads to exacerbated aflatoxin production to varying degrees among diverse isolates of Aspergillus flavus. To take advantage of this observation and investigate this system as a potential avenue of mitigating aflatoxin contamination, a combination of genetic engineering and genomics has been employed. Genetic engineering approaches were done including transgenic overexpression and CRISPR-Cas9-mediated silencing for antioxidant genes in maize and peanut. Genotypic and phenotypic evaluation of effects on plant ROS accumulation, drought tolerance, and aflatoxin resistance is ongoing. In addition, to explore stress-linked mechanisms in A. flavus related to host resistance, a pair of reference genomes for A. flavus isolates with contrasting growth behavior, stress tolerance, and aflatoxin production were de novo assembled using Pacbio long-read sequencing and Bionano optical mapping. These represent the first pseudomolecule-level genomes produced for this important pathogen. Comparative analyses with other re-sequenced, diverse isolates as well as examining the effects of oxidative stress on early signaling events will also be discussed.