Deblur is a novel method for resolving single-nucleotide community sequence patterns in microbial studies. It uses error profiles to obtain putative error-free sequences from Illumina sequencing platforms. Deblur reduces computational demands compared to similar methods while maintaining or improving sensitivity and specificity. It is effective in detecting closely related bacterial sequences with single nucleotide differences, removing false positives, and maintaining stability in detection. Deblur operates on a per-sample level, making it scalable for large datasets and meta-analyses. It is open-source under the BSD license and can be used to integrate data from multiple sequencing rounds of the American Gut Project. Deblur provides a rapid and sensitive means to assess ecological patterns driven by differentiation of closely related taxa. It is applicable to large-scale sequencing data sets and can integrate sequencing runs collected over time. Deblur is more stable than DADA2 and UNOISE2, especially at higher frequency thresholds. It is faster and more memory-efficient than DADA2 and UNOISE2. Deblur is released under the BSD license, allowing easy commercial adoption and peer scrutiny. It is positioned to operate on present and future large-data sets as well as continued discovery through reuse of existing rich data sets.Deblur is a novel method for resolving single-nucleotide community sequence patterns in microbial studies. It uses error profiles to obtain putative error-free sequences from Illumina sequencing platforms. Deblur reduces computational demands compared to similar methods while maintaining or improving sensitivity and specificity. It is effective in detecting closely related bacterial sequences with single nucleotide differences, removing false positives, and maintaining stability in detection. Deblur operates on a per-sample level, making it scalable for large datasets and meta-analyses. It is open-source under the BSD license and can be used to integrate data from multiple sequencing rounds of the American Gut Project. Deblur provides a rapid and sensitive means to assess ecological patterns driven by differentiation of closely related taxa. It is applicable to large-scale sequencing data sets and can integrate sequencing runs collected over time. Deblur is more stable than DADA2 and UNOISE2, especially at higher frequency thresholds. It is faster and more memory-efficient than DADA2 and UNOISE2. Deblur is released under the BSD license, allowing easy commercial adoption and peer scrutiny. It is positioned to operate on present and future large-data sets as well as continued discovery through reuse of existing rich data sets.