The complete genome sequence of *Streptococcus mutans* UA159, a serotype c strain, has been determined, revealing a circular chromosome of 2,030,936 base pairs. The genome contains 1,963 ORFs, with 63% assigned putative functions. The analysis provides insights into how *S. mutans* adapts to the oral environment through resource acquisition, defense against host factors, and maintenance of its niche against microbial competitors. The strain can metabolize a wide variety of carbohydrates via nonoxidative pathways, with all pathways and associated transport systems identified. Virulence genes related to extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains genes essential for competence and quorum sensing. Mobile genetic elements, including a conjugative transposon and a composite transposon containing genes for gramicidin/bactaracin synthesis, are prominent in the genome, but no bacteriophage genomes are present. The genome sequence offers a basis for future drug development and new approaches to prevent and treat dental caries.The complete genome sequence of *Streptococcus mutans* UA159, a serotype c strain, has been determined, revealing a circular chromosome of 2,030,936 base pairs. The genome contains 1,963 ORFs, with 63% assigned putative functions. The analysis provides insights into how *S. mutans* adapts to the oral environment through resource acquisition, defense against host factors, and maintenance of its niche against microbial competitors. The strain can metabolize a wide variety of carbohydrates via nonoxidative pathways, with all pathways and associated transport systems identified. Virulence genes related to extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains genes essential for competence and quorum sensing. Mobile genetic elements, including a conjugative transposon and a composite transposon containing genes for gramicidin/bactaracin synthesis, are prominent in the genome, but no bacteriophage genomes are present. The genome sequence offers a basis for future drug development and new approaches to prevent and treat dental caries.