Direct instruction is a proven effective method to strengthen children’s ability to design unconfounded experiments using the control-of-variables strategy (CVS). Recent research suggests that task segmentation can also promote children’s use of this strategy. The present study investigated this assumption by comparing the relative effectiveness of both instructional approaches in elementary science classes. Children in the direct instruction condition (n = 22) were taught the CVS prior to investigating a multivariable inquiry task. Children in the task structuring condition (n = 23) were not, but received a segmented version of the inquiry task that addressed the variables in successive order. Children in the control condition (n = 22) investigated the multivariable inquiry task without additional support. Comparison among these three conditions revealed that task structuring equals direct instruction in effectiveness to promote children to use the CVS and draw valid inferences, and that either type of guidance is more effective than unguided inquiry learning. However, as children’s knowledge of the CVS improved as much in either condition, more practice seems needed for children to take full advantage of both instructional approaches.