Genome editing can be associated with genotoxicity, which must be carefully evaluated before gene-edited products can be used clinically. We have recently described CAST-Seq, a diagnostic assay for the genome-wide detection of CRISPR-Cas-induced chromosomal aberrations. The method is based on the detection of chromosomal rearrangements resulting from the simultaneous cleavage of the on-target and an off-target site. While CAST-Seq is able to identify CRISPR-Cas nuclease-induced chromosomal aberrations with high sensitivity, the sensitivity to detect off-target activity of base editors or prime editors is lower because these editing platforms do not rely on the formation of DNA double-strand breaks. In addition, in rare cases, designing effective CAST-Seq primers for a specific target site in GC-rich regions of the genome can be tedious. To overcome these limitations, we developed universal CAST-Seq (U-CAST), a method for detecting off-target activities of any CRISPR-based editing platform without the need for primer optimization. U-CAST is based on the fact that any DNA double-strand break can serve as an "anchor" to detect off-target events triggered by any genome/base/prime editor. Using U-CAST to identify the off-target activities of CRISPR-Cas9 nuclease and base editors, all targeting the same site in the EMX1 gene, revealed that the evoCDA1-BE4max base editor generated more off-target mutagenesis than Cas9 nuclease, while the next-generation CBE-T1.52 base editor effectively mitigated off-target effects. Because the method can be performed with already established U-CAST primers, U-CAST saves time and costs, and is particularly well suited for screening genome and base editors in early development.