As our understanding of the brain’s physiology and pathology progresses, increasingly sophisticated materials and technologies are required to advance discoveries in systems neuroscience and develop more effective diagnostics and treatments for neuropsychiatric disease. Localizing brain signals may assist with tissue resection and intervention strategies in patients with such diseases. Precise localization requires large and continuous coverage of cortical areas with high-density recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic electronic–based, conformable neural interface device (NeuroGrid) with embedded integrated circuitry capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety recording with such devices in anesthetized and awake subjects. Highly localized and traveling physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrid technology to disorders such as epilepsy may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.