Understanding how biological systems evolve across changing conditions has been a crucial focus of research. Mutations change the genetic context in which genes are expressed and yet the mechanisms underlying mutation fitness are still unclear. We use the sweet corn mutant sugary1 (su1) as a model for understanding the genetic regulation of mutant fitness, focusing on the mutant × genotype interaction across diverse environments. In a previous work, we identified quantitative trait loci (QTLs) affecting fitness in a mapping population of recombinant inbred lines (RILs) derived from a cross between field corn (B73) × sweet corn (P39 or IL14h) parents; however, the epistatic effects of these QTLs on su1 fitness were not investigated. In the present study, we estimated fitness for two seed production environments. Viability of su1 is under genetic and environmental controls, regulated by multiple genes with minor contributions, and these genes depend on the genotype into which the mutation is introduced and on the environment. Some QTLs were in linkage disequilibrium with the maize gene Su1 and had epistatic effects on su1 fitness. These QTLs could be used by sweet corn breeders by combining the most favorable alleles associated with su1 viability in breeding new genotypes from field × sweet corn crosses. These results also have implications for mutagenesis breeding or genome editing because the epistatic effects of the target genome on the new alleles generated by these techniques could affect the success of the breeding program.