Leaf rust (Puccinia triticina) is one of the three major rust diseases of wheat (Triticum aestivum). We tested the ability of foliar sprays derived from aqueous leaf extracts of Jacaranda mimosifolia (Bignoniaceae), Thevetia peruviana (Apocynaceae) and Calotropis procera (Apocynaceae) to protect wheat from leaf rust. Extracts from all three species inhibited P. triticina spore germination in vitro. Plants sprayed with extracts before inoculation developed significantly lower levels of disease incidence (percentage of total number of plants infected) than unsprayed, inoculated controls. Sprays combining 0.6% leaf extracts and 2 mM salicylic acid with the fungicide Amistar Xtra at 0.05% (10 µg/L azoxystrobin + 4 µg/L cyproconazole) were significantly more effective in reducing disease incidence than sprays of higher concentrations (0.1%) of fungicide alone. Extracts of J. mimosifolia were most active, either alone (1.2%), or in lower doses (0.6%) in combination with lower rates (0.05%) of Amistar Xtra. Measurement of relative transcript abundance by RT-qPCR of a set of nine defence-related genes encoding chitinase, β-1,3-glucanase, peroxidase, phenylalanine ammonia lyase and PR-proteins revealed that leaf extracts combined with fungicide strongly stimulated defence-related gene expression and the subsequent accumulation of PR proteins in the apoplast of inoculated wheat leaves. The level of protection afforded was significantly correlated with the ability of extracts to increase PR protein expression. We conclude that foliar pre-treatment of wheat with formulations containing previously untested plant leaf extracts enhances the level of protection against leaf rust provided by fungicide sprays, offering an alternative to disease management based only on fungicides.