AbstractAmbipolar organic electrochemical transistors (OECTs) with a single organic mixed ionic‐electronic conductor (OMIEC) have unique advantages by reducing fabrication complexity and cost in complementary logic circuit and bioelectronic applications. However, the design and synthesis of high‐performance ambipolar OMIECs for efficient transport and coupling both cation/anion and electron/hole remain challenging. Herein, a donor–acceptor (D–A)‐typed ambipolar OMIEC polymer (DHF‐gTT) is presented, whose superior ambipolarity stems from the concurrent oligoethyleneglycol‐functionalized D/A units that facilitates cation/anion injection and transport. Additionally, the fluorination of acceptor unit improves both hole/electron transports due to the fully‐locked backbone and promotes electron injection by down‐shifting molecular energy levels. Consequently, DHF‐gTT‐based OECTs achieve balanced figure‐of‐merit (µC*) for both p‐type and n‐type operations (12.4–14.6 F cm−1 V−1 s−1), setting new benchmarks for ambipolar OECTs, in terms of n‐type µC* and electron/hole mobilities. Such ambipolar OECTs enable the inverter to achieve a record‐high gain (102 V/V) and associated n‐type and p‐type molecular detectors to offer real‐time and highly sensitive detection of histamine and hydrogen peroxide detection, respectively. These results indicate the effectiveness of judicious molecular design on achieving high‐performance ambipolar OMIECs, allowing the state‐of‐the‐art single‐component ambipolar OECTs for both highly integrated logic circuit and bioelectronic applications.