Upconversion nanocrystals (UCNCs) have recently been explored as optical imaging nanoprobes. However, conventional β-NaLuF4- based UCNCs often suffer from large particle size and weak upconversion luminescence (UCL) intensity, leading to poor biocompatibility and low detection sensitivity. Here, a novel strategy for controlling the crystalline phase and size of UCNCs has been developed by doping of yttrium ions, resulting in particle size reduction and phase transition. The total UCL intensity of prepared core–shell UCNCs is significantly enhanced up to ≈4.9 and ≈17.4 times after Tm3+and Er3+ doping than that of core UCNCs, offering deeper tissue UCL imaging with a depth of 8 mm in vivo. Moreover, the CT signal of core–shell UCNCs is ≈1.5 and ≈3.5 times brighter than that of core UCNCs and commercial ioversol agent because of increasing contents of Lu3+ doped in UCNCs. The synthesized core–shell UCNCs hold a great promise in deep UCL and CT dual-modality imaging in vitro and in vivo.