New genomic resources and genetic tools of the past few years have advanced the nematode genus Caenorhabditis as a model for comparative biology. However, understanding of natural genetic variation at molecular and phenotypic levels remains rudimentary for most species in this genus, and for C. briggsae in particular. Here we characterize phenotypic variation in C. briggsae’s sensitivity to the potentially important and variable environmental toxin, ethanol, for globally diverse strains. We also quantify nucleotide variation in a new sample of 32 strains from four continents, including small islands, and for the closest-known relative of this species (C. sp. 9). We demonstrate that C. briggsae exhibits little heritable variation for the effects of ethanol on the norm of reaction for survival and reproduction. Moreover, C. briggsae does not differ significantly from C. elegans in our assays of its response to this substance that both species likely encounter regularly in habitats of rotting fruit and vegetation. However, we uncover drastically more molecular genetic variation than was known previously for this species, despite most strains, including all island strains, conforming to the broad biogeographic patterns described previously. Using patterns of sequence divergence between populations and between species, we estimate that the self-fertilizing mode of reproduction by hermaphrodites in C. briggsae likely evolved sometime between 0.9 and 10 million generations ago. These insights into C. briggsae’s natural history and natural genetic variation greatly expand the potential of this organism as an emerging model for studies in molecular and quantitative genetics, the evolution of development, and ecological genetics.