Widespread planting of crops genetically modified to express Bacillus thuringiensis (Bt) toxins for pest control may potentially affect nontarget pests and soil-borne disease. In this study, a field trial was conducted to explore the effects of habitat diversification, specifically an intraspecies mixture of genetically distinct cotton lines, on nontarget pests and soil-borne disease. It was hypothesized that the mixture would suppress disease severity and would alter pest and predator abundances. Results confirmed that a row-mixture of 75% insect-resistant cotton and 25% disease-resistant cotton suppressed Fusarium wilt and controlled cotton aphids. However, intercropping at the genotypic level increased mirid bug and sweetpotato whitefly densities in cotton. Moreover, the effect of the mixture on predator abundance ranged from neutral to positive and was highly variable among species and years. Species-specific pest responses to the crop mixture provide new insights for optimally sized and configured refuge construction in the future.