The CRISPR-Cas9 system enables facile and efficient genome engineering in living cells and organisms. Small molecule control of CRISPR-Cas9 would allow precise temporal control in applications of the technology. In this work, we developed s[combining low line]mall m[combining low line]olecule-activated allosteric a[combining low line]ptamer r[combining low line]egulat[combining low line]ing (SMART)-sgRNAs as general strategies to control programmable genome editing. With SMART-sgRNAs, temporal control of the CRISPR-Cas9 system against different targets can be achieved, which should facilitate its application in various fields, such as biomedical genome editing, drug screening and chromosome imaging.