<p>Humans can selectively follow one voice amid competing sounds, an ability that is essential for everyday communication. Previous studies show that this cocktail party effect depends on hierarchical brain processing, but it remains unclear how spatially directed listening shapes this process. Here, we show that selective attention to speech from one side is associated with a contralateral pattern of neural synchronization during listening. Using functional magnetic resonance imaging in a spatial listening task, we find that attending to speech on the left is linked to stronger synchronization between the speaker’s mouth motor region and the listener’s right auditory and higher-level cortical regions, as well as stronger synchronization between the speech signal and these same regions; the opposite pattern is observed when attention is directed to the right. Unattended speech, by contrast, is associated with more limited synchronization that is largely restricted to the listener’s auditory cortex. Better listening performance is also specifically related to activity in higher-level regions opposite the attended side. These findings show that spatially guided selective listening organizes speech processing through a contralateral synchronization mechanism and provide a framework for understanding how the brain separates competing speech in real-world environments.</p>