Al–Li alloys with high elastic modulus, low density and high specific strength have been widely used in aerospace industry. However, although Al3Li precipitates enhance the strength significantly, the appearance of shearable Al3Li precipitates usually decreases the ductility, leading to the strength-ductility trade-off. In this study, the strategy of microalloying is applied to fabricate an Al–2.46 Li–0.2 Sc (wt.%) alloy with tunable precipitate sizes by heat treatment. This alloy exhibits a good combination of strength and ductility when the precipitate radius is smaller than 6.7 nm or larger than 16.4 nm. The strengthening mechanisms in Al–Li–Sc alloy with different precipitate sizes are quantitatively discussed. With the increase of precipitate size, the dominant precipitation strengthening mechanism changes. The influence of precipitate on ductility is mainly achieved by influencing the dynamic recovery rate of dislocation which can be illustrated by a dislocation-based model. When the precipitate size is relatively small or large, the Al–Li–Sc alloy exhibits a higher ductility owing to a lower dynamic recovery rate. This study provides insight for understanding the strength and ductility in Al–Li–Sc alloy as well as potential theoretical guideline for designing novel high-performance Al–Li based alloys.