Lead and mercury are among the most dangerous environmental pollutants due to their high toxicity to humans and other living organisms. They are also ubiquitous in our ecosystems as a result of industrial waste. Therefore, it is essential to develop a simple and inexpensive method to rapidly detect low concentrations of these metals in various liquids, including wastewater. Aptamer-based electrolyte-gated organic field-effect transistors (EGOFETs), which are traditionally used to detect large biomolecules such as viruses and proteins, are a promising concept for heavy-metal detection. To achieve this, we chose several aptamers with high affinity for and specificity to Pb²⁺ and Hg²⁺ ions, determined the dissociation constants and stoichiometry of the complexes, investigated the kinetics of complex formation and cross-specificity and proposed structures for the aptamer–cation complexes. Based on these aptamers, we developed EGOFET-based aptasensors for Pb²⁺ and Hg²⁺. The fabricated EGOFET devices have been shown to be sensitive to low concentrations of lead (from 30 nM to 2.5 μM) and mercury (from 250 nM to 2.5 μM) cations. These ranges correspond to the maximum permissible concentrations in drinking and wastewater for lead, which are 144 nM and 1.2 μM, respectively, and exceed the range of maximum permissible concentration in drinking and wastewater for mercury, which is 5 nM. Despite this, it was possible to detect mercury cations at a concentration of 5 nM within five minutes in a model system that simulates liquid flow using the EGOFET device. This demonstrates the potential for fast and selective detection of Pb²⁺ and Hg²⁺ ions at maximum permissible concentrations in drinking water using EGOFET-based aptasensors. This is a significant step forward in the development of flow sensors for detecting heavy metals in liquid media.