Bicyclo[1.1.1]pentanes (BCPs) are important bioisosteres of aryl, tert-butyl groups, and internal alkynes that can impact key physicochemical properties on drug candidates. Herein, we describe a novel and efficient reaction to synthesize alkyl-alkynyl-substituted BCP derivatives by synergistic photoredox and copper catalysis at room temperature. The mild reaction conditions, simple protocol, broad functional group tolerance, and high efficiency of this procedure make it a valuable strategy for accessing alkynyl-substituted BCPs.