Ti2AlNb intermetallic alloy is highly suitable for aerospace key component manufacturing due to its low density, exceptional temperature strength, high specific strength, and creep resistance. However, the poor machining quality and severe tool wear appear, because of their poor thermal conductivity and excellent high temperature strength performance. In this paper, the coated and uncoated end mills are performed to investigate the tool wear characteristics during side milling of Ti2AlNb intermetallic alloys. In addition, the milling forces, tool service life, tool wear morphologies and mechanisms are discussed in detail. Results indicate that the coated and uncoated end mills suffered severe tool wear in the side milling process, leading to a rapid increase in milling forces. The coated end mill exhibited a longer service life of tools than the uncoated end mill. The service life of coated end mill reaches 6 min, primarily limited by flank wear and accompanied by chipping, whereas the uncoated end mill had a service life restricted to 2 min due to tool tip breakage. Tool wear morphologies of coated and uncoated end mills include rake face wear and flank face wear. Typical characteristics (e.g., crater wear, built-up edge, chipping and adhesion) are observed on the rake face of the both coated and uncoated end mills. On the flank face of the coated end mill, the chip adhesion, micro-chipping, chipping and coating delamination are found, whereas only chip adhesion and micro-chipping appear for uncoated end mill. Furthermore, the primary mechanisms of wear for both coated and uncoated end mills are adhesive wear and oxidation wear, which occur on both the rake face and flank face.