Halobacterium sp. strain BOL4-2 was isolated from an Andean salt flat, Salar de Uyuni, in Bolivia. Single-molecule real-time (SMRT) sequencing revealed a 2.4-Mbp genome with a 2.0-Mbp chromosome and four plasmids (2 to 299 kb). Its isolation from an environment experiencing multiple extremes makes the strain interesting for astrobiology.