CRISPResso2 is a software tool for the comprehensive analysis, visualization, and comparison of sequencing data from genome editing experiments. It introduces five key innovations: (1) comprehensive analysis of sequencing data from base editors; (2) batch mode for analyzing and comparing multiple editing experiments; (3) allele-specific quantification of heterozygous or polymorphic references; (4) a biologically-informed alignment algorithm; and (5) ultra-fast processing time. CRISPResso2 allows users to quantify and visualize amplicon sequencing data from base editing experiments. It takes raw FASTQ files as input and outputs reports on base editing activity frequencies and efficiencies, plots showing base substitutions across the entire amplicon region, and nucleotide substitution frequencies for a user-specified region. It also produces publication-quality plots for nucleotides of interest with heatmaps showing conversion efficiency. The tool improves processing time and memory usage to enable analysis of hundreds of genome editing experiments using batch functionality. It generates intuitive plots to show nucleotide frequencies and indel rates at each position in each sample. In cases where the genome editing target contains more than one allele, CRISPResso2 enables allelic-specific quantification by aligning individual reads to each allelic variant and assigning each read to the most closely-aligned allele. The tool also improves the alignment algorithm to increase the accuracy of indel calling and produce alignments that reflect the current understanding of the editing mechanism. It was tested using simulations and found to accurately recover editing events with a negligible false-positive rate. CRISPResso2 is a faster, more accurate, and efficient tool for analyzing genome editing data.CRISPResso2 is a software tool for the comprehensive analysis, visualization, and comparison of sequencing data from genome editing experiments. It introduces five key innovations: (1) comprehensive analysis of sequencing data from base editors; (2) batch mode for analyzing and comparing multiple editing experiments; (3) allele-specific quantification of heterozygous or polymorphic references; (4) a biologically-informed alignment algorithm; and (5) ultra-fast processing time. CRISPResso2 allows users to quantify and visualize amplicon sequencing data from base editing experiments. It takes raw FASTQ files as input and outputs reports on base editing activity frequencies and efficiencies, plots showing base substitutions across the entire amplicon region, and nucleotide substitution frequencies for a user-specified region. It also produces publication-quality plots for nucleotides of interest with heatmaps showing conversion efficiency. The tool improves processing time and memory usage to enable analysis of hundreds of genome editing experiments using batch functionality. It generates intuitive plots to show nucleotide frequencies and indel rates at each position in each sample. In cases where the genome editing target contains more than one allele, CRISPResso2 enables allelic-specific quantification by aligning individual reads to each allelic variant and assigning each read to the most closely-aligned allele. The tool also improves the alignment algorithm to increase the accuracy of indel calling and produce alignments that reflect the current understanding of the editing mechanism. It was tested using simulations and found to accurately recover editing events with a negligible false-positive rate. CRISPResso2 is a faster, more accurate, and efficient tool for analyzing genome editing data.