An accurate three-dimensional (3D) segmentation of the maxillary sinus is crucial for multiple diagnostic and treatment applications. Yet, it is challenging and time-consuming when manually performed on a cone-beam computed tomography (CBCT) dataset. Recently, convolutional neural networks (CNNs) have proven to provide excellent performance in the field of 3D image analysis. Hence, this study developed and validated a novel automated CNN-based methodology for the segmentation of maxillary sinus using CBCT images. A dataset of 264 sinuses were acquired from 2 CBCT devices and randomly divided into 3 subsets: training, validation, and testing. A 3D U-Net architecture CNN model was developed and compared to semi-automatic segmentation in terms of time, accuracy, and consistency. The average time was significantly reduced (p-value < 2.2e-16) by automatic segmentation (0.4 min) compared to semi-automatic segmentation (60.8 min). The model accurately identified the segmented region with a dice similarity co-efficient (DSC) of 98.4%. The inter-observer reliability for minor refinement of automatic segmentation showed an excellent DSC of 99.6%. The proposed CNN model provided a time-efficient, precise, and consistent automatic segmentation which could allow an accurate generation of 3D models for diagnosis and virtual treatment planning.