A facile, general, and economical synthesis of diversely functionalized pyrimidines has been realized under basic conditions via the copper-catalyzed cyclization of ketones with nitriles. The reaction proceeds via a novel pathway involving the nitriles acting as electrophiles and consecutive C-C bond and two C-N bond formations and shows broad substrate scope and good tolerance of many important functional groups. This strategy represents a new platform for constructing pyrimidine structures.