In this work, we pursue a unified paradigm for multimodal pretraining to break the scaffolds of complex task/modality-specific customization. We propose OFA, a unified multimodal pretrained model that unifies modalities (i.e., cross-modality, vision, language) and tasks (e.g., image generation, visual grounding, image captioning, image classification, text generation, etc.) to a simple sequence-tosequence learning framework based on the encoder-decoder architecture. OFA performs pretraining and finetuning with task instructions and introduces no extra task-specific layers for finetuning. Experimental results show that OFA achieves new state-of-the-arts on a series of multimodal tasks, including image captioning (COCO test CIDEr: 149.6), text-to-image generation (COCO test FID: 10.5), VQA (test-std acc.: 80.02), SNLI-VE (test acc.: 90.20), and referring expression comprehension (RefCOCO / RefCOCO+ / RefCOCOg test acc.: 92.93 / 90.10 / 85.20). Through extensive analyses, we demonstrate that OFA reaches comparable performance with uni-modal pretrained models (e.g., BERT, MAE, MoCo v3, SimCLR v2, etc.) in uni-modal tasks, including NLU, NLG, and image classification, and it effectively transfers to unseen tasks and domains. Code shall be released soon at https://github.com/OFA-Sys/OFA.