The controllable growth of two-dimensional (2D) semiconductors with large domain sizes and high quality is much needed in order to reduce the detrimental effect of grain boundaries on device performance but has proven to be challenging. Here, we analyze the precursor concentration on the substrate surface which significantly influences nucleation density in a vapor deposition growth process and design a confined micro-reactor to grow 2D In2Se3 with large domain sizes and high quality. The uniqueness of this confined micro-reactor is that its size is ~102-103 times smaller than that of a conventional reactor. Such a remarkably small reactor causes a very low precursor concentration on the substrate surface, which reduces nucleation density and leads to the growth of 2D In2Se3 grains with sizes larger than 200 μm. Our experimental results show large domain sizes of the 2D In2Se3 with high crystallinity. The flexible broadband photodetectors based on the as-grown In2Se3 show rise and decay times of 140 ms and 25 ms, efficient response (5.6 A/W), excellent detectivity (7×1010 Jones), high external quantum efficiency (251%), good flexibility, and high stability. This study, in principle, provides an effective strategy for the controllable growth of high quality 2D materials with few grain boundaries.