In everyday life, we are continuously struggling at focusing on our current goals while at the same time avoiding distractions. Attention is the neuro-cognitive process devoted to the selection of behaviorally relevant sensory information while at the same time preventing distraction by irrelevant information. Distraction can be prevented proactively, by strategically prioritizing task-relevant information at the expense of irrelevant information, or reactively, by suppressing the ongoing processing of distractors. The distinctive neuronal signature of these suppressive mechanisms is still largely unknown. Thanks to machine-learning decoding methods applied to prefrontal cortical activity, we monitor the dynamic spatial attention with an unprecedented spatial and temporal resolution. We first identify independent behavioral and neuronal signatures for long-term (learning-based spatial prioritization) and short-term (dynamic spatial attention) mechanisms. We then identify distinct behavioral and neuronal signatures for proactive and reactive suppression mechanisms. We find that while distracting task-relevant information is suppressed proactively, task-irrelevant information is suppressed reactively. Critically, we show that distractor suppression, whether proactive or reactive, strongly depends on the implementation of both long-term and short-term mechanisms of selection. Overall, we provide a unified neuro-cognitive framework describing how the prefrontal cortex deals with distractors in order to flexibly optimize behavior in dynamic environments.