Technical Abstract: •Climate change (altered CO2, warming, and precipitation) may affect plant–microbial interactions, such as the Lolium arundinaceum–Neotyphodium coenophialum symbiosis, to alter future ecosystem structure and function. •To assess this possibility, tall fescue tillers were collected from an existing climate manipulation experiment in a constructed old-field community in Tennessee (USA). Endophyte infection frequency (EIF) was determined, and infected (E+) and uninfected (E-) tillers were analysed for tissue chemistry. •The EIF of tall fescue was higher under elevated CO2 (91% infected) than with ambient CO2 (81%) but was not affected by warming or precipitation treatments. Within E+ tillers, elevated CO2 decreased alkaloid concentrations of both ergovaline and loline, by c. 30%; whereas warming increased loline concentrations 28% but had no effect on ergovaline. Independent of endophyte infection, elevated CO2 reduced concentrations of nitrogen, cellulose, hemicellulose, and lignin. •These results suggest that elevated CO2, more than changes in temperature or precipitation, may promote this grass–fungal symbiosis, leading to higher EIF in tall fescue in old-field communities. However, as all three climate factors are likely to change in the future, predicting the symbiotic response and resulting ecological consequences may be difficult and dependent on the specific atmospheric and climatic conditions encountered.