Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a major disease of winter wheat that occurs frequently in the central and southeastern United States. Quantitative resistance to SNB in wheat is determined by various disease resistance components and their interaction with environmental factors. A study was conducted in North Carolina from 2018 to 2020 to characterize SNB lesion size and growth rate and to quantify the effects of temperature and relative humidity on lesion expansion in winter wheat cultivars with different levels of resistance. Disease was initiated in the field by spreading P. nodorum-infected wheat straw in experimental plots. Cohorts (groups of foliar lesions arbitrarily selected and tagged as an observational unit) were sequentially selected and monitored throughout each season. Lesion area was measured at regular intervals, and weather data were collected using in-field data loggers and the nearest weather stations. Final mean lesion area was approximately seven times greater on susceptible than on moderately resistant cultivars, and lesion growth rate was approximately four times higher on susceptible than on moderately resistant cultivars. Across trials and cultivars, temperature had a strong effect of increasing lesion growth rates ( P < 0.001), while relative humidity had no significant effect ( P = 0.34). Lesion growth rate declined slightly and steadily over the duration of cohort assessment. Our results demonstrate that restricting lesion growth is an important component of SNB resistance in the field and suggest that the ability to limit lesion size may be a useful breeding goal.