Metal nanoparticles are widely studied due to their various applications, such as their potential use in the control of phytopathogens and the promotion of plant growth, with a significant impact on agriculture. Various microbial metabolites are used to reduce and stabilize metals and metal oxides to the nanoscale. In the present work, the biological synthesis of silver and copper oxide nanoparticles using Trichoderma harzianum TA2 is reported. The nanoparticles were purified and characterized with complementary methodologies to obtain information on the size, distribution, morphology, surface charge, and functional groups of the nanoparticles. The in vitro antifungal activity of the nanoparticles against pathogens of rice and wheat, as well as their effect on seed germination, were evaluated. In general, the nanoparticles showed a spherical shape, an average size of 17–26 nm, and low polydispersity. Furthermore, they showed antifungal activity at low concentrations against Sclerotium oryzae (0.140 M), Rhizoctonia oryzae-sativae (0.140 M), Fusarium graminearum (0.034 M), and Pyricularia oryzae (0.034 M). The germination of seeds treated with nanoparticles was not negatively affected. This is the first report of biogenic silver and copper oxide nanoparticles from a single strain of T.harzianum with antifungal activity against four phytopathogens of interest in Uruguay. Furthermore, the synthesis of the biogenic nanoparticles was faster and more efficient than previous reports using other fungi. In conclusion, this work reveals that biogenic metallic nanoparticles from T. harzianum TA2 can be considered as candidates for the control of phytopathogens affecting important crops.