Distinguishing structural isomers is a critical and challenging task for biotechnology, chemical industry, and environmental monitoring. Approaches currently available are limited in terms of selectivity and simplicity. In this paper, a highly sensitive organic field‐effect transistor (OFET) using the cyclopentadithiophene‐benzothiadiazole (CDT‐BTZ) copolymers as a semiconductor is presented for easy and selective detection of different families of structural isomers, as well as between different isomers within each family. High accuracy discrimination is achieved over a range of concentrations using only a single sensing parameter derived from the OFET characteristic transfer curve. As a reference, other homopolymer‐ and donor–acceptor copolymer‐based OFET sensors are examined but do not have an equivalent sensing performance to that of the CDT‐BTZ‐based OFETs. Investigating the link between isomer absorption and swelling, supramolecular order and energy levels of the active layer reveals a unique effect of each isomer on the energy bands of the semiconducting polymer.