The rice endophyte Harpophora oryzae shares a common pathogenic ancestor with the rice blast fungus Magnaporthe oryzae. Direct comparison of the interactions between a single plant species and two closely-related (1) pathogenic and (2) mutualistic fungi species can improve our understanding of the evolution of the interactions between plants and fungi that lead to either mutualistic or pathogenic interactions. Differences in the metabolome and transcriptome of rice in response to challenge by H. or M. oryzae were investigated with GC-MS, RNA-seq, and qRT-PCR. Levels of metabolites of the shikimate and lignin biosynthesis pathways increased continuously in the M. oryzae-challenged rice roots (Mo-roots); these pathways were initially induced, but then suppressed, in the H. oryzae-challenged rice roots (Ho-roots). Compared to control samples, concentrations of sucrose and maltose were reduced in the Ho-roots and Mo-roots. The expression of most genes encoding enzymes involved in glycolysis and the TCA cycle were suppressed in the Ho-roots, but enhanced in the Mo-roots. The suppressed glycolysis in Ho-roots would result in the accumulation of glucose and fructose which was not detected in the Mo-roots. A novel co-evolution pattern of fungi-host interaction is proposed which highlights the importance of plant host in the evolution of fungal symbioses.