We conducted two experiments, one long term with a 2¿C increase (Experiment 1) and one short term with a 4.4¿C increase (Experiment 2), to investigate main and interactive effects of warming, clipping, and doubled precipitation on soil CO2 efflux and its temperature sensitivity in a U.S. tallgrass prairie. On average, warming increased soil CO2 efflux by 13.0% (p < 0.01) in Experiment 1, by 22.9% (p < 0.0001) in Experiment 2, and by 26.6% (p < 0.0001) in the transient study of Experiment 2. Doubled precipitation resulted in an increase of 9.0% (p < 0.05) in soil CO2 efflux in Experiment 2. Yearly clipping did not significantly affect soil CO2 efflux (p = 0.66) in Experiment 1, while clipping decreased soil CO2 efflux by 16.1% (p < 0.05) in the transient study. Temperature sensitivity of soil CO2 efflux significantly decreased from an apparent Q10 value of 2.51 in unwarmed plots to 2.02 in warmed plots without extra precipitation and from 2.57 to 2.23 with doubled precipitation in Experiment 2. No significant interactive effects among the experimental factors were statistically found on soil CO2 efflux or their temperature sensitivities except for the warming ¿ clipping interaction (p < 0.05) in the transient study. Our observed minor interactive effects relative to main ones suggest that results from single-factor experiments are useful in informing us of potential responses of soil CO2 efflux to multifactor global change, at least in our ecosystem.