The traditional method of gene deletion in prokaryotes involves transforming cells with a recombinant selectable marker that replaces a gene of interest. However, this method often leads to a merodiploid state in prokaryotes, such as the model archaeon Pyrococcus furiosus, that contain multiple copies of their chromosome. A subset of chromosomes acquires the marker while others retain the targeted gene, requiring weeks of passaging to produce loss-of-function mutants. P. furiosus encodes sequence-specific DNA-targeting CRISPR-Cas systems, which confer adaptive immunity against genetic invaders. In this study, we harness the endogenous CRISPR-Cas systems of P. furiosus to accelerate genome modification. Inserting a synthetic CRISPR mini-array into the genome through recombination allows CRISPR-Cas systems to target unmodified chromosome copies, achieving gene deletion in one week. Scarless knockouts can be achieved through each individual CRISPR-Cas system in P. furiosus. We use this approach to delete three genes simultaneously – a process traditionally requiring many months.