Wheat blast caused by the Magnaporthe oryzae Triticum (MoT) pathotype is one of the most damaging fungal diseases of wheat. During the screening of novel bioactive secondary metabolites, we observed two marine secondary metabolites, bonactin and feigrisolide C, extracted from the marine bacteria Streptomyces spp. (Act 8970 and ACT 7619), remarkably inhibited the hyphal growth of an MoT isolate BTJP 4 (5) in vitro. In a further study, we found that bonactin and feigrisolide C reduced the mycelial growth of this highly pathogenic isolate in a dose-dependent manner. Bonactin inhibited the mycelial development of BTJP 4 (5) more effectively than feigrisolide C, with minimal concentrations for inhibition being 0.005 and 0.025 µg/disk, respectively. In a potato dextrose agar (PDA) medium, these marine natural products greatly reduced conidia production in the mycelia. Further bioassays demonstrated that these secondary metabolites could inhibit the MoT conidia germination, triggered lysis, or conidia germinated with abnormally long branched germ tubes that formed atypical appressoria (low melanization) of BTJP 4 (5). Application of these natural products in a field experiment significantly protected wheat from blast disease and increased grain yield compared to the untreated control. As far as we are aware, this is the first report of bonactin and feigrisolide C that inhibited mycelial development, conidia production, conidial germination, and morphological modifications in the germinated conidia of an MoT isolate and suppressed wheat blast disease in vivo. To recommend these compounds as lead compounds or biopesticides for managing wheat blast, more research is needed with additional MoT isolates to identify their exact mode of action and efficacy of disease control in diverse field conditions.