Underground carbon dioxide (CO2) sequestration is widely accepted as a proven and established technology to respond to global warming from greenhouse gas emissions. It is crucial to monitor the CO2 plume effectively throughout the life cycle of a geologic CO2 sequestration project to ensure safety and storage efficacy. We propose a fast and efficient deep learning workflow for near real-time data assimilation, forecasting and visualization of CO2 plume evolution in saline aquifer and demonstrate its application at a field site.Our proposed workflow integrates field measurements, including distributed pressure and temperature at wells to visualize spatial and temporal migration of the CO2 plume in the subsurface. The deep learning framework has two key concepts that enhance the efficiency of the training and robustness of the CO2 plume prediction: first, instead of using multiple saturation images as output of the deep-learning model, a single Time of Flight (TOF) image are used to represent CO2 plume propagation; second, we use variational autoencoder-decoder (VAE) for high dimensional image data compression considering uncertainties in the predicted images. Time-of-Flight (TOF) is the travel time of a neural particle from the injection point, which is calculated along streamline based on the velocity field by considering reservoir heterogeneity and driving forces. The latent variables of VAE are estimated through a deep neural network model with inputs of distributed pressure and temperature measurements. Subsequently, the decoder part of the VAE expands the estimated latent variables to the original dimension of the TOF images. We demonstrate the efficacy of the proposed method by comparison with the more traditional pareto-based multi-objective Genetic Algorithm (MOGA) for the assimilation of the field measurements and forecasting of the CO2 plume migration.The power and utility of our proposed workflow are demonstrated by application to the Illinois Basin-Decatur Project (IBDP). The IBDP is a large scale 3-year CO2 storage test and is part of the Midwest Regional Carbon Sequestration Partnership (MRCSP). The field measurements include bottom-hole pressure and distributed temperature sensing (DTS) data at the injection well, and the distributed pressure measurements at several locations along the monitoring well. The dynamic model is a compositional model with 1.7 million cells. First, we identify the influential parameters using sensitivity analysis based on the pressure and temperature responses. Next, the sensitive parameters are sampled from a pre-specified range and a comprehensive training dataset is generated, including the pressure and temperature measurements and TOF images based on flow simulation results from a variety of geological model realizations. The trained neural network model can identify geological model realizations that capture the spatial and temporal migration of pressure and CO2 saturation based on Euclidean distance within the VAE latent space. For comparison with traditional history matching workflow, the selected sensitive parameters are also tuned using MOGA with the pressure and temperature measurements. A reasonable agreement is obtained for the predicted CO2 plume migration between two workflows. The proposed deep learning workflow shows significant speed-up compared to the traditional multi-objective optimization-based history matching workflow (5 h for training and seconds for prediction; compared to several days/weeks for the MOGA).The novelty of this work is the application of an efficient deep learning-based workflow to a large-scale CO2 storage test site for assimilating field measurements and predicting CO2 plume propagation in a near real-time and comparison with traditional history matching approach.