Animals continuously encounter heterogenous mixtures of multiple chemicals that fluctuate in their concentrations and temporal properties, and inform them of the presence and location of food, mates, competitors, and predators. To correctly decode this information, chemosensory responses must not only be robust and sensitive, but must also be highly flexible. Animals integrate information such as internal state and contextual cues in order to modulate their responses even to cues that are innately attractive (such as those from food), or aversive (such as those from toxic substances). Using high-resolution microfluidics behavioral assays and in vivo calcium imaging, we describe a mechanism by which C. elegans switches its behavioral preference for a subset of food-related odors from strong attraction to strong repulsion based on odorant context. We find that this behavioral switch is driven by a switch in the sign of the response to these odorants in a single olfactory neuron type, and identify signal transduction molecules that mediate this response plasticity. Our results indicate that a food-related chemical can evoke bidirectional sensory responses and drive behavioral plasticity via context-dependent engagement of distinct intracellular signaling pathways in a single sensory neuron type. Funded by the NSF.