We studied the spatial and temporal distribution of third-instar Musca domestica L. in three high-rise poultry facilities in central Pennsylvania, and investigated its relation to manure moisture. Autocorrelograms, a geostatistical index, revealed pronounced spatial autocorrelation in M. domestica, with ranges of spatial structure from 13 to 117 m. Under normal field conditions, we observed a nonlinear functional relationship between manure moisture and larval abundance, and empirically derived an optimal manure moisture range of 74–78%. The abundance of third instars was significantly positively correlated with manure moisture at the same location in space and time for approximately half of the sampling intervals. However, moisture measurements were generally spatially random at scales ≥4 m, and thus do little to explain the spatial structure of M. domestica. Also, we rarely observed significant correlation between moisture and larval abundance over discrete temporal lags ≥7 d. However, atypical field conditions, resulting in moisture measurements that were abnormally high or low, were observed to dictate larval population dynamics over time by rendering manure habitats unfavorable for natural enemy establishment or to fly propagation, respectively.