Targeted enrichment of conserved genomic regions is a popular method for collecting large amounts of sequence data from non-model taxa for phylogenetic, phylogeographic, and population genetic studies. Yet, few open-source workflows are available for identifying conserved genomic elements shared among divergent taxa and designing enrichment baits targeting these regions. These shortcomings limit the application of targeted enrichment methods to many organismal groups. Here, I describe a universal approach for identifying conserved genomic regions in available genomic sequences and designing targeted enrichment baits to collect data from these conserved regions. I demonstrate how this computational approach can be applied to diverse organismal groups by identifying sets of conserved loci and designing enrichment baits targeting these loci in the understudied arthropod orders Arachnida, Coleoptera, Diptera, Hemiptera, or Lepidoptera. I then use in silico analyses to demonstrate that these conserved loci reconstruct the accepted relationships among genomes sequences from the focal arthropod orders. We perform in vitro validation of the Arachnid probe set as part of a separate manuscript in this issue (Starrett et al. ). All of the documentation, software code, and probe sets developed here are available under an open-source license for further, restriction-free testing and use by any research group, and although the examples in this manuscript focus on understudied and exceptionally diverse arthropod groups, the software workflow is applicable to all organismal groups having some form of pre-existing genomic information.