Humans require the ability to discriminate intensities of noxious stimuli to avoid future harm. This discrimination process seems to be biased by an individual's attention to pain and involves modulation of the relative intensity differences between stimuli (ie, Weber fraction). Here, we ask whether attention networks in the brain modulate the discrimination process and investigate the neural correlates reflecting the Weber fraction for pain intensity. In a delayed discrimination task, participants differentiated the intensity of 2 sequentially applied stimuli after a delay interval. Compared with nonpain discrimination, pain discrimination performance was modulated by participants' vigilance to pain, which was reflected by the functional connectivity between the left inferior parietal lobule and the right thalamus. Of note, this vigilance-related functional coupling specifically predicted participants' behavioral ability to differentiate pain intensities. Moreover, unique to pain discrimination tasks, the response in the right superior frontal gyrus linearly represented the Weber fraction for pain intensity, which significantly biased participants' pain discriminability. These findings suggest that pain intensity discrimination in humans relies on vigilance-related enhancement in the parieto-thalamic attention network, thereby allowing the prefrontal cortex to estimate the relative intensity differences between noxious stimuli.