Bordetella pertussis is the main cause of whooping cough, a disease that still infects millions of individuals annually despite widespread vaccination. This is particularly problematic in neonates, where infection can lead to death. Endemicity, subclinical infections and circulation of multiple lineages hide the underlying dynamics of Bordetella pertussis from surveillance systems. Therefore, the extent of its spread across spatial scales remains unknown, as does the role of vaccines in driving changes in strain fitness. In this thesis, I investigate the spatial spread and fitness changes of Bordetella pertussis through the development of mathematical models that integrate the information provided by genetic data. I start by investigating Bordetella pertussis geographical spread. I found substantial diversity within communities, consistent with widespread subclinical transmission. I quantified the rate of Bordetella pertussis spread across spatial scales and found that it spreads between countries and between continents in just a few years. I then investigated the fitness of Bordetella pertussis genotypes and the impact of vaccine type switch. I developed an analytical framework that quantifies the relative fitness of different circulating genotypes through time. I found that the implementation of acellular vaccines was associated to large-scale changes in fitness and can explain long-term genotype dynamics. Finally, I explored Bordetella pertussis fitness beyond its known genotypes. I developed an agnostic framework that summarises the changes in population composition in phylogenetic trees through time. It allows for the automatic detection of circulating lineages based on differences in fitness, which can be quantified and linked back to specific mutations. I applied this method to Bordetella pertussis genomes from four countries and detected the presence of multiple co-circulating lineages with underlying differences in fitness, none of which have been previously identified. The insights gained into Bordetella pertussis spatial dynamics and its interactions with vaccine-induced immunity are highly relevant to vaccination policies. This thesis addresses fundamental questions about drivers of spread and fitness that are relevant across disease systems and control efforts.