A flexible computational platform, comprising both a command-line set of tools and a C++ API, for the analysis and manipulation of high-throughput sequencing data such as DNA-seq, RNA-seq, ChIP-seq and MethylC-seq. GenomicTools implements a variety of mathematical operations between sets of genomic regions thereby enabling the prototyping of computational pipelines that can address a wide spectrum of tasks ranging from pre-processing and quality control to meta-analyses. Additionally, the GenomicTools platform is designed to analyze large datasets of any size by minimizing memory requirements. Where directly comparable, we evaluated the time and memory performance of GenomicTools against (i) the IRanges Bioconductor package and (ii) the BEDTools suite. In overlap computations, GenomicTools outperforms IRanges and BEDTools with an average 9.1 and 3.6 speedup, respectively in sorted data with a minimal memory footprint.