IT IS NOTICEABLE that Cephalosporium maydis causes late wilt disease that is considered sole of the ultimate destructive diseases in Zea maize. The crop output is declined due to the infection riskiness raises. Silver nanoparticles (AgNPs) were prepared using a simple bio-reduction method, which is ecologically welcomed and cost-effective. In our investigation, the effect the antifungal activity of AgNPs was evaluated alone or combined with one of each two different fungicides on C. maydis in vitro and in vivo. An isolate of Aspergillus niger previously isolated and identified in our laboratory was used to induce AgNPs. The NPs production,s undergone to optimization study for increasing AgNPs product besides its stability. AgNPs production after optimization showed very stable product compared with those before optimization conditions. A significant increase in the absorbance was noticed from 0.8OD into 1.25OD and the NPs size decreased from 19nm into 9nm. In addition, TEM showed more obvious and clear AgNPs, in addition, a higher degree of stability and protein functional surface reactive groups at (-29.3mv) with single peak was revealed for six months. Under laboratory conditions, the higher rate of growth inhibition of C. maydis was obvious in case of using AgNPs either alone or combined with fungicides. Parallel results were found under greenhouse conditions where AgNPs caused a severe reduction in disease severity of C. maydis infected plants accounting (57.7%) alone or combined with Maxim XL (75.5%) or Vitavax (90%). This research opens up new possibilities in the field of using AgNPs in plant disease treatment.