Oxathiapiprolin is a new fungicide with extremely high efficacy against oomycete plant pathogens. Solo components oxathiapiprolin (OXPT), chlorothalonil (CHT), azoxystrobin (AZ), mandipropamid (MPD), and mefenoxam (MFX) were compared with each other and with four oxathiapiprolin pre-packed fungicidal mixtures, OXPT+CHT 1+66.7, OXPT+AZ 1+10.3, OXPT+MPD 1+8.3, and OXPT+MFX 1+3 (weight active ingredient ratio), for control efficacy of late blight induced by MFX-insensitive Phytophthora infestans strains in tomato in growth chambers and the field. Mixtures performed better than all partner fungicides alone, except OXPT. Of the four mixtures, OXPT+MFX outperformed, with the highest preventive, curative, translaminar, and systemic efficacies. In the field, OXPT+MFX was superior to other fungicides in controlling late blight epidemics induced by MFX-insensitive isolates. Its deployment in the field will combat the dominating MFX-insensitive isolates, reduce the selection pressure imposed on P. infestans and delay the buildup of subpopulations resistant to oxathiapiprolin.