A ligand-controlled and site-selective nickel catalyzed Suzuki–Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp²)–C(sp³) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)–C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)–O bond, which later generates the ketone product.