The hermetic sealing of optoelectronic devices has attracted much attention because it can endow the devices with long-term operation reliability and high mechanical resistance. Herein, we present a facile and efficacious strategy for fabrication of water-resistant and highly adhesive acrylate-based sealing materials for hermetic optical devices using oxime-based photoinitiators. Compared with conventional sealing materials containing ketone-based photoinitiator, those embedded with oxime-based photointiators afforded a strong UV absorption in the effective wavelength range, a high UV curing conversion of 99.5% at a low radiant energy of 1.0 J cm-2, a remarkable adhesion strength of 42.2 kgf cm-2, an improved water impermeability of 5.3 g m?2 day-1, and a reduced internal pollution length of 104.9 μm. These excellent properties of the fabricated sealing materials are attributed to the fragmentation mechanism of oxime-based photoinitiators which can generate numerous initiating radicals through multi-step decomposition reactions, resulting in the efficient initiation for photoreaction with acrylate resins. This study provides promising sealing materials based on the oxime-based photoinitiators for ultra-slim and flexible optoelectronic applications.