Advanced human cognition is attributed to increased neocortex size and complexity, but the underlying gene regulatory mechanisms are unknown. Using deep learning model of embryonic neocortical enhancers, and human and macaque embryonic neocortex H3K27ac data, we identified ~4000 enhancers gained in the human, largely attributable to single-nucleotide essential mutations. The genes near gained enhancers exhibit increased expression in human embryonic neocortex, and are involved in critical neural developmental processes, and are expressed specifically in the progenitor cells and interneurons. The gained enhancers, especially the essential mutations, are associated with central nervous system disorders/traits. The essential mutations establish enhancer activities through affecting binding of key transcription factors of embryonic neocortex. Overall, our results suggest that non-coding mutations have led to de novo enhancer gains in the embryonic human neocortex, that orchestrate the expression of genes involved in critical developmental processes associated with human cognition.