MOTIVATION: Whole-genome bisulfite sequencing is a powerful tool for analyzing chromatin methylation genome-wide, but analysis of whole-genome bisulfite data is slow, inflexible, and often inaccurate. RESULTS: We developed PCBS (Principal Component BiSulfite), a computationally efficient R package for Whole Genome Bisulfite Sequencing analysis that demonstrates remarkable accuracy and flexibility compared to current tools. PCBS identifies differentially methylated loci, differentially methylated regions, and offers novel functionality that allows for more targeted methylation analyses. PCBS uses minimal computational resources; a complete pipeline in mouse can run on a local RStudio instance in a matter of minutes. AVAILABILITY AND IMPLEMENTATION: PCBS is an R package available under a GNU GPLv3 license on GitHub: https://github.com/katlande/PCBS and CRAN: https://CRAN.R-project.org/package=PCBS. Instructions for use are available at: https://katlande.github.io/PCBS/.