Significance Precisely defining specific cell types is critical but challenging for biological studies. Site-specific tyrosine-recombinase Cre and its inducible variants have been widely used in efficient genetic engineering. However, a single recombinase system has technical hurdles. Here, a photoactivatable Dre (PA-Dre) recombinase is developed by tethering split Dre fragments to the light-inducible Magnets system. PA-Dre is efficient and stringently controlled in vitro and in vivo. Moreover, with the creation of the Cre-activated light-inducible Dre system, it is able to achieve bulk or sparse labeling of specific neurons in a spatiotemporal manner. This flexible and tunable system could be adapted to a wide range of biological systems for the modulation of developmental and genetic complexity.