Helicobacter pylori is a genetically diverse and coevolved pathogen inhabiting human gastric niches and leading to a spectrum of gastric diseases in susceptible populations. We describe the genome sequence of H. pylori 908, which was originally isolated from an African patient living in France who suffered with recrudescent duodenal ulcer disease. The strain was found to be phylogenetically related to H. pylori J99, and its comparative analysis revealed several specific genome features and novel insertion-deletion and substitution events. The genome sequence revealed several strain-specific deletions and/or gain of genes exclusively present in HP908 compared with different sequenced genomes already available in the public domain. Comparative and functional genomics of HP908 and its subclones will be important in understanding genomic plasticity and the capacity to colonize and persist in a changing host environment.