Abstract Motivation Advances in genomics and sequencing technologies demand faster and more scalable analysis methods that can process longer sequences with higher accuracy. However, classical pairwise alignment methods, based on dynamic programming (DP), impose impractical computational requirements to align long and noisy sequences like those produced by PacBio and Nanopore technologies. The recently proposed wavefront alignment (WFA) algorithm paves the way for more efficient alignment tools, improving time and memory complexity over previous methods. However, high-performance computing (HPC) platforms require efficient parallel algorithms and tools to exploit the computing resources available on modern accelerator-based architectures. Results This paper presents WFA-GPU, a GPU (graphics processing unit)-accelerated tool to compute exact gap-affine alignments based on the WFA algorithm. We present the algorithmic adaptations and performance optimizations that allow exploiting the massively parallel capabilities of modern GPU devices to accelerate the alignment computations. In particular, we propose a CPU–GPU co-design capable of performing inter-sequence and intra-sequence parallel sequence alignment, combining a succinct WFA-data representation with an efficient GPU implementation. As a result, we demonstrate that our implementation outperforms the original multi-threaded WFA implementation by up to 4.3× and up to 18.2× when using heuristic methods on long and noisy sequences. Compared to other state-of-the-art tools and libraries, the WFA-GPU is up to 29× faster than other GPU implementations and up to four orders of magnitude faster than other CPU implementations. Furthermore, WFA-GPU is the only GPU solution capable of correctly aligning long reads using a commodity GPU. Availability and implementation WFA-GPU code and documentation are publicly available at https://github.com/quim0/WFA-GPU.