The development of hydrogen sulfide (H2S) sensors is essential to address H2S‐related pharmacology since slow‐releasing H2S medications have been identified to be prospective options for cancer treatments. Here, we described an electrochemical sensor for highly selective and sensitive detection of aqueous H2S, using a thin film of fumarate‐based face‐ centered cubic (fcu)‐based metal–organic frameworks (fum‐fcu‐MOF) modified on laser‐scribed graphene (LSGE). The fum‐fcu‐MOF has shown a strong affinity and chemical stability to H2S analysis. The electrochemical and H2S catalytic properties were studied for fum‐fcu‐MOF/ LSGE. An amperometry and differential pulse voltammetry techniques were demonstrated to validate the sensor. The resulting sensor delivered acceptable analytical parameters in terms of; detection limit (3.0 µM), dynamic range (10–500 µM), reproducibility, and stability (94.7%). The sensor's practical validity was demonstrated in bacterial cells and H2S‐ releasing drug, where the sensor was able to monitor the continuous release of in‐situ H2S. The pharmacokinetics of a slow releasing H2S donor is accessed at different time intervals and different concentration levels. Our research indicate that this fum‐fcu‐MOF based H2S sensor holds potential in understanding pharmacokinetics of H2S releasing drugs.