With the increasing concerns for the environment and the progress in non-invasive diagnosis, monitoring volatile organic compounds (VOCs) have attracted considerable attention. Ammonia and acetone are of particular interest because they are related to chronic kidney disease and diabetes disorder, respectively. Multi-functional donor-acceptor conjugated polymers are potential candidates for building reliable ammonia and acetone sensors due to the recent advance in the field of thin film transistor. In this report, we demonstrate that the transistor mobility, the device stability and the sensitivity of sensors can be greatly enhanced by incorporating functional groups directly on the polymer main chain. The fluorinated isoindigo polymers exhibit hole mobility with over an order improvement than their un-fluorinated counterparts. The novel polymer transistors sensor can discriminate various VOCs and detect 100 ppb ammonia gas and 50 ppm acetone gas within 2 min in air. This is the most sensitive polymer transistor-based sensor towards acetone ever reported. The influence of fluorination is systematic studied to understand the intermolecular interaction between the analytes and fluorine atoms. Exceptional sensitivity to ammonia is attributed to the hydrogen bond forming between fluorine and ammonia and the sensitivity to acetone is due to the changing in the energy levels of frontier orbitals of the polymers. Fluorination of conjugated polymers enhance the transistor and gas sensing performance, which is essential for building fast response and high sensitivity sensor platform.