Registration and fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) of the prostate can provide guidance for prostate brachytherapy. However, accurate registration remains a challenging task due to the lack of ground truth regarding voxel-level spatial correspondence, limited field of view, low contrast-to-noise ratio, and signal-to-noise ratio in TRUS. In this study, we proposed a fully automated deep learning approach based on a weakly supervised method to address these issues. We employed deep learning techniques to combine image segmentation and registration, including affine and nonrigid registration, to perform an automated deformable MRI-TRUS registration. To start with, we trained two separate fully convolutional neural networks (CNNs) to perform a pixel-wise prediction for MRI and TRUS prostate segmentation. Then, to provide the initialization of the registration, a 2D CNN was used to register MRI-TRUS prostate images using an affine registration. After that, a 3D UNET-like network was applied for nonrigid registration. For both the affine and nonrigid registration, pairs of MRI-TRUS labels were concatenated and fed into the neural networks for training. Due to the unavailability of ground-truth voxel-level correspondences and the lack of accurate intensity-based image similarity measures, we propose to use prostate label-derived volume overlaps and surface agreements as an optimization objective function for weakly supervised network training. Specifically, we proposed a hybrid loss function that integrated a Dice loss, a surface-based loss, and a bending energy regularization loss for the nonrigid registration. The Dice and surface-based losses were used to encourage the alignment of the prostate label between the MRI and the TRUS. The bending energy regularization loss was used to achieve a smooth deformation field. Thirty-six sets of patient data were used to test our registration method. The image registration results showed that the deformed MR image aligned well with the TRUS image, as judged by corresponding cysts and calcifications in the prostate. The quantitative results showed that our method produced a mean target registration error (TRE) of 2.53 ± 1.39 mm and a mean Dice loss of 0.91 ± 0.02. The mean surface distance (MSD) and Hausdorff distance (HD) between the registered MR prostate shape and TRUS prostate shape were 0.88 and 4.41 mm, respectively. This work presents a deep learning-based, weakly supervised network for accurate MRI-TRUS image registration. Our proposed method has achieved promising registration performance in terms of Dice loss, TRE, MSD, and HD.