Current PEFT methods for LLMs can achieve either high quality, efficient training, or scalable serving, but not all three simultaneously. To address this limitation, we investigate sparse fine-tuning and observe a remarkable improvement in generalization ability. Utilizing this key insight, we propose a family of Structured Sparse Fine-Tuning (S$^{2}$FT) methods for LLMs, which concurrently achieve state-of-the-art fine-tuning performance, training efficiency, and inference scalability. S$^{2}$FT accomplishes this by "selecting sparsely and computing densely". It selects a few heads and channels in the MHA and FFN modules for each Transformer block, respectively. Next, it co-permutes weight matrices on both sides of the coupled structures in LLMs to connect the selected components in each layer into a dense submatrix. Finally, S$^{2}$FT performs in-place gradient updates on all submatrices. Through theoretical analysis and empirical results, our method prevents forgetting while simplifying optimization, delivers SOTA performance on both commonsense and arithmetic reasoning with 4.6% and 1.3% average improvements compared to LoRA, and surpasses full FT by 11.5% when generalizing to various domains after instruction tuning. Using our partial backpropagation algorithm, S$^{2}$FT saves training memory up to 3$\times$ and improves latency by 1.5-2.7$\times$ compared to full FT, while delivering an average 10% improvement over LoRA on both metrics. We further demonstrate that the weight updates in S$^{2}$FT can be decoupled into adapters, enabling effective fusion, fast switch, and efficient parallelism for serving multiple fine-tuned models.