There has been much interest in analyzing genome-scale DNA sequence data to infer population histories, but the inference methods developed hitherto are limited in model complexity and computational scalability. Here, we present an efficient, flexible statistical method that can utilize whole-genome sequence data from multiple populations to infer complex demographic models involving population size changes, population splits, admixture, and migration. We demonstrate through an extensive simulation study that our method can accurately and efficiently infer demographic parameters in realistic biological scenarios. The algorithms described here are implemented in a new version of the software package diCal, which is available for download at https://sourceforge.net/projects/dical2.