Genome sequence analysis is fundamental to medical breakthroughs such as developing vaccines, enabling genome editing, and facilitating personalized medicine. The exponentially expanding sequencing datasets and complexity of sequencing algorithms necessitate performance enhancements. While the performance of software solutions is constrained by their underlying hardware platforms, the utility of fixed-function accelerators is restricted to only certain sequencing algorithms.This paper presents QUETZAL, the first general-purpose vector acceleration framework designed for high efficiency and broad applicability across a diverse set of genomics algorithms. While a commercial CPU’s vector datapath is a promising candidate to exploit the data-level parallelism in genomics algorithms, our analysis finds that its performance is often limited due to long-latency scatter/gather memory instructions. QUETZAL introduces a hardware-software co-design comprising an accelerator microarchitecture closely integrated with the CPU’s vector datapath, alongside novel vector instructions to fully capitalize on the proposed hardware. QUETZAL integrates a set of scratchpad-style buffers meticulously designed to minimize latency associated with scatter/gather instructions during the retrieval of input genome sequences data. QUETZAL supports both short and long reads, and different types of sequencing data formats. A combination of hardware and software techniques enables QUETZAL to reduce the latency of memory instructions, perform complex computation using a single instruction, and transform data representations at runtime, resulting in overall efficiency gain. QUETZAL significantly accelerates a vectorized CPU baseline on modern genome sequence analysis algorithms by 5.7×, while incurring a small area overhead of 1.4% post place-and-route at the 7nm technology node compared to an HPC ARM CPU.