Ni-catalyzed Sonogashira coupling of nonactivated, β-H- containing alkyl halides, including chlorides, is reported. The coupling is tolerant to a wide range of functional groups, including ether, ester, amide, nitrile, keto, heterocycle, acetal, and aryl halide, in both coupling partners. The coupling can be selective for a specific C−X bond (X = I, Br, Cl) and allows for orthogonal functionalization of alkyl halides with multiple reactive sites.