Climate change scenarios predict the North American Great Plains to experience decreases in annual average precipitation and fewer but more intense storms. These trends will cause greater variation in water availability likely affecting microbially-mediated soil carbon cycling. Our goal was to address how drying interval and differences in historical precipitation regime affect grassland soil microbial responses to wet-up. Soils with long-term (17y) manipulated precipitation timing regimes from the Rainfall Manipulation Plots (RaMPs) experiment at Konza Prairie Biological Station were collected. The field experimental treatments contrast historically “Ambient” conditions reflecting precipitation occurring on site and “Altered” conditions that have periods between rainfall extended 50% over ambient intervals with all rainfall from that period applied in one pulse. These soils were incubated in the laboratory for 25 d, and repeatedly dried and re-wet to 3 different soil volumetric water contents (25%, 16%, 9% VWC; short, intermediate, and long interval treatments). Sterile tap water was added to bring soils to the time-zero VWC (38%, control incubations held constant at this level). We hypothesized that after dry-down and subsequent wet-up, drought resilient taxa would increase in abundance corresponding with higher microbial biomass C (MBC) and carbon use efficiency (CUE). We also expected that long interval Altered soils would hold the highest proportion of resilient taxa and exhibit higher microbial CUE, analogous to results from field wet-up experiments. During the lab incubation period, control treatments showed that soils with Ambient field precipitation history had a higher respiration rate compared to Altered precipitation history (respectively 26.5 > 20.7 μg CO2-C·g-1 soil·h-1, P < 0.01). Following the final wet-up, MBC increased regardless of laboratory drying interval or historical precipitation regime (0.69 > 0.51 mg MBC·g-1 soil, P < 0.01). CUE was greater in short-interval soils compared to long-interval (respectively 0.69 > 0.44, P = 0.05), but did not differ between historical field treatments. Over the full incubation period, less total carbon was mineralized in Altered compared to Ambient soils in all laboratory treatments (P < 0.01) but drying interval did not affect total carbon mineralized. Preliminary bacterial community analyses suggest that the dominant bacterial OTUs (100 most abundant) are primarily drought tolerant (i.e., no change in relative abundance prior to and following wet-up across drying interval treatments). However, a small proportion of dominant OTUs were drought resilient (2%, 5%) and intolerant (1%, 2%) in Ambient and Altered soils. These data support the hypothesis that microbial communities are functionally resilient to drought stress. Contrary to our hypothesis, CUE was lower in long interval soils and not affected by historical precipitation regime suggesting an important influence of plant-microbial interactions in situ on microbial carbon cycling responses to dynamic soil water conditions.