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The aboveground fresh weight of weeds is an important indicator that reflects their biomass and physiological activity and directly affects the criteria for determining the amount of herbicides to apply. In precision agriculture, the development of models that can accurately locate weeds and predict their fresh weight can provide visual support for accurate, variable herbicide application in real time. In this work, we develop a two-stream dense feature fusion convolutional network model based on RGB-D data for the real-time prediction of the fresh weight of weeds. A data collection method is developed for the compilation and production of RGB-D data sets. The acquired images undergo data enhancement, and a depth transformation data enhancement method suitable for depth data is proposed. The main idea behind the approach in this study is to use the YOLO-V4 model to locate weeds and use the two-stream dense feature fusion network to predict their aboveground fresh weight. In the two-stream dense feature fusion network, DenseNet and NiN methods are used to construct a Dense-NiN-Block structure for deep feature extraction and fusion. The Dense-NiN-Block module was embedded in five convolutional neural networks for comparison, and the best results were achieved with DenseNet201. The test results show that the predictive ability of the convolutional network using RGB-D as the input is better than that of the network using RGB as the input without the Dense-NiN-Block module. The mAP of the proposed network is 75.34% (IoU value of 0.5), the IoU is 86.36%, the detection speed of the fastest model with a RTX2080Ti NVIDIA graphics card is 17.8 fps, and the average relative error is approximately 4%. The model proposed in this paper can provide visual technical support for precise, variable herbicide application. The model can also provide a reference method for the non-destructive prediction of crop fresh weight in the field and can contribute to crop breeding and genetic improvement.