Benefiting from molecular design and device innovation, electronic devices based on polymer semiconductors have achieved significant developments and gradual commercialization over the past few decades. Most of high-performance polymer semiconductors that have been prepared exhibit p-type performances, and records of their carrier mobilities are constantly being broken through. Although ambipolar and n-type polymers are necessary for constructing p-n heterojunctions and logic circuits, only a few materials show outstanding device performances, which leads to their developments lagging far behind that of p-type analogues. As a consequence, it is extremely significant to summarize polymer semiconductors with excellent electron transport performances. This review focuses on the design considerations and bonding modes between monomers of polymer semiconductors with high electron mobilities. To enhance electron transport performances of polymer semiconductors, the structural modification strategies are described in detail. Subsequently, the electron transport, thermoelectric, mixed ionic-electronic conduction, intrinsically stretchable, photodetection, and spin transport performances of high-electron mobility polymers are discussed from the perspective of molecular engineering. In the end, the challenges and prospects in this research field are presented, which provide valuable guidance for the design of polymer semiconductors with excellent electron transport performances and the exploration of more advanced applications in the future.