Inactivation of Gli3, a key component of Hedgehog signaling in vertebrates, results in formation of additional digits (polydactyly) during limb bud development. The analysis of mouse embryos constitutively lacking Gli3 has revealed the essential GLI3 functions in specifying the anteroposterior (AP) limb axis and digit identities. We conditionally inactivated Gli3 during mouse hand plate development, which uncoupled the resulting preaxial polydactyly from known GLI3 functions in establishing AP and digit identities. Our analysis revealed that GLI3 directly restricts the expression of regulators of the G1–S cell-cycle transition such as Cdk6 and constrains S phase entry of digit progenitors in the anterior hand plate. Furthermore, GLI3 promotes the exit of proliferating progenitors toward BMP-dependent chondrogenic differentiation by spatiotemporally restricting and terminating the expression of the BMP antagonist Gremlin1. Thus, Gli3 is a negative regulator of the proliferative expansion of digit progenitors and acts as a gatekeeper for the exit to chondrogenic differentiation. Display omitted ► Formation of extra anterior digits is uncoupled from anteroposterior patterning ► GLI3 curbs digit progenitor proliferation by directly regulating cell-cycle entry ► GLI3 initiates BMP-dependent chondrogenesis by timely terminating Grem1 expression ► GLI3 restricts digit number to five by dual control of growth and differentiation GLI3 is an important regulator of digit number in tetrapods. Lopez-Rios et al. reveal the dual mechanism by which GLI3 directly restricts cell-cycle entry and proliferation and promotes BMP-dependent exit of digit progenitors to chondrogenesis. In Gli3-deficient hand plates, additional digits form due to aberrant growth rather than defective patterning.