The overuse of antibiotics makes its detection very significant for human health. New facile methods and high‐performance sensory materials will be urgently needed for detection of antibiotics. Unfortunately, there are few reports on fluorescence enhancement of antibiotics detection. Herein, based on the modulability of the coordination mode, we proposed two MOFs with different coordination modes based on different metal ions: Zn‐MOF (1) and Cd‐MOF (2). The fluorescence of 1 and 2 can be efficiently and selectively quenched by nitrofuran antibiotics (nitrofurazone, NFZ and furazolidone, FZD) and chloramphenicol (CAP), respectively. Particularly, the matched energy levels between 2 and enrofloxacin (ENR) enables 2 with turn‐on sensing for ENR. Moreover, apart from the sensitivity and selectivity, 1 and 2 also have strong recyclable ability, fast response time and anti‐interference ability, which make them great potential sensory materials to detect antibiotics.