Tall fescue (Schedonurus arundinaceus), an exotic invasive grass in North America, can associate with a fungal endophyte that causes livestock toxicity. Native prairies are frequently managed with interactive fire and grazing, yet little is known regarding tall fescue's endophytic and toxicological responses. From 2012 to 2014, we applied patch-burn grazing (PBG—burning a different third annually) or graze and burn (GAB—burning completely in 2012 but no fire in 2013 or 2014) treatments to tall fescue–invaded grasslands. Burning happened in March/April, and cattle grazing occurred during the growing season. Tall fescue tillers were analyzed for Epichloë endophyte presence and alkaloid concentrations (ergovaline, ergovalinine, N-acetylnorloline, N-formylloline, N-acetylloline). Cattle toxicosis was assessed via fecal ergovaline levels. With PBG, tiller defoliation was greater in burned patches versus unburned and was greater than any years in GAB. In GAB, tiller defoliation was no different the year of the burn than the years without fire. Cattle did not discriminate between endophyte-infected or endophyte-free tillers in either treatment. Endophyte infection levels were inversely related to years since fire (YSF), and various alkaloids displayed asynchronous responses to YSF. Cattle had no detectable fecal ergovaline when managed with patchy or complete pasture fires. Only two herds had detectable fecal ergovaline (> 100 ppb), which were in pastures managed without fire and only in 2013. Thus, patch burning tall fescue–invaded grasslands alters alkaloids and tiller defoliation with implications for cattle toxicosis. Future research should incorporate greater intra-annual resolution of plant phenology relative to focal grazing and alkaloid expression.