Late blight caused by the oomycete Phytophthora infestans is considered the biggest threat to potato farming worldwide. For susceptible cultivars, the disease is often managed by frequent applications of fungicides to reduce yield loss. The use of bio-based compounds that interfere with biologically active systems is an innovative strategy for improving disease management. In the present work, the control of P. infestans infection on potatoes by potassium phosphite (KPhi) combined with recommended and reduced doses of active ingredients (Ais) from different fungicides was evaluated. The protective effects of different combinations were initially assessed in vivo and subsequently compared with a greenhouse screening. The active ingredients cyazofamid (CFD) and mancozeb (MCB), used at recommended and reduced doses, were less effective at reducing P. infestans infections than when combined with KPhi. In greenhouse trials, CFD, mandipropamid (MPD) and MCB at recommended doses were the most effective treatments when combined with KPhi; meanwhile, the combination of KPhi with azoxystrobin (AZ), benthiavalicarb-isopropyl/mancozeb (ISO/MCB), and CFD at reduced doses exhibited strong protective activity compared to other similar combinations. This decreased the severity of infection by P. infestans up to ~89%. Greenhouse experiments also demonstrated that a combination of KPhi and CFD at both doses caused the highest reduction in disease severity (up to ~90%) within 35 days of infection. In microplot experiments, KPhi delayed the progression of late blight in susceptible potato varieties; therefore, in the combined treatments AUDPC values were significantly lower than those obtained after applications with CFD doses, providing sufficient protection against late blight. Our data suggest that optimizing the formulation with addition of KPhi could result in a lower recommended dose. This would result in a reduction of the active compounds of the fungicides in potato farming. Furthermore, the impact of KPhi on late blight development makes it a potential component for incorporation into an integrated pest management system.