Abstract The Pacific geoduck Panopea generosa (class Bivalvia, order Adapedonta, family Hiatellidae, genus Panopea) is the largest known burrowing bivalve with considerable commercial value. Pacific geoduck and other geoduck clams play important roles in maintaining ecosystem health for their filter feeding habit and coupling pelagic and benthic processes. Here, we report a high-quality chromosome-level genome assembly of P. generosa to characterize its phylogeny and molecular mechanisms of its life strategies. The assembled P. generosa genome consists of 19 chromosomes with a size of 1.47 Gb, a contig N50 length of 1.6 Mb, and a scaffold N50 length of 73.8 Mb. The BUSCO test of the genome assembly showed 93.0% completeness. Constructed chromosome synteny revealed many occurrences of inter- and intrachromosomal rearrangements between P. generosa and Sinonovacula constricta. Of the 35,034 predicted protein-coding genes, 30,700 (87.6%) could be functionally annotated in public databases, indicating the high quality of genome annotation. Comparison of gene copy numbers of gene families among P. generosa and 11 selected species identified 507 rapidly expanded P. generosa gene families that are functionally enriched in immune and gonad development and may be involved in its complex survival strategies. In particular, genes carrying the copine domains underwent additional duplications in P. generosa, which might be important for neuronal development and immune response. The availability of a fully annotated chromosome-level genome provides a valuable dataset for genetic breeding of P. generosa.