Fusarium avenaceum is the predominant fungal pathogen responsible for root rot in Angelica crops and poses a serious threat to their commercial quality and yield in China. This fungus produces enniatin B (ENN B), a toxin that could be a pathogenicity and virulence factor in plant–pathogen interactions. Yet whether ENN B exacerbates host infection and the onset of root rot in Angelica spp. caused by F. avenaceum is surprisingly understudied. Pathogenicity assays revealed that ENN B co-inoculation with F. avenaceum significantly increased the root rot disease index in Angelica sinensis from 83.33% (pathogen alone) to 92.86% (p < 0.05). Toxin degradation experiments showed that the bacteria Paenibacillus polymyxa and Bacillus tequilensis were capable of degrading 60.69% and 70.02% of ENN B, respectively. Response surface optimization (24.5 °C, 22.01 mg/L ENN B, 0.99% inoculum) enhanced degradation by B. tequilensis to 81.94%, a 11.74% improvement. Three ester compounds were identified by LC-HRMS as potential degradation products of ENN B. In planta trials demonstrated that the disease index was 50.01% for the group co-inoculated with ENN B degradation products and F. avenaceum, a 42.85% reduction compared to the group co-inoculated with ENN B and F. avenaceum. This study provides a new microbial strategy for controlling root rot in Angelica crops from a mycotoxin degradation perspective, which can be applied to promote sustainable agricultural production.