The 2016 M_w 5.8 Pawnee earthquake occurred in a region with active wastewater injection into a basal formation group. Prior to the earthquake, fluid injection rates at most wells were relatively steady, but newly collected data show significant increases in injection rate in the years leading up to earthquake. For the same time period, the total volumes of injected wastewater were roughly equivalent between variable‐rate and constant‐rate wells. To understand the possible influence of these changes in injection, we simulate the variable‐rate injection history and its constant‐rate equivalent in a layered poroelastic half‐space to explore the interplay between pore‐pressure effects and poroelastic effects on the fault leading up to the mainshock. In both cases, poroelastic stresses contribute a significant proportion of Coulomb failure stresses on the fault compared to pore‐pressure increases alone, but the resulting changes in seismicity rate, calculated using a rate‐and‐state frictional model, are many times larger when poroelastic effects are included, owing to enhanced stressing rates. In particular, the variable‐rate simulation predicts more than an order of magnitude increase in seismicity rate above background rates compared to the constant‐rate simulation with equivalent volume. The observed cumulative density of earthquakes prior to the mainshock within 10 km of the injection source exhibits remarkable agreement with seismicity predicted by the variable‐rate injection case.