Upon his arrival at Stanford, he began a collaboration with Edward Tatum, who had been working with Neurospora crassa since 1941 in collaboration with George Beadle. In this way, he was connected to the very earliest research with Neurospora. Throughout his career, he continued to work with Neurospora crassa, which he often championed as a model organism. At the time that he died in 2007, a substantial percentage of all researchers in the world who were working with Neurospora crassa had either trained with or collaborated with Perkins or one of his students or associates.

Perkins is best known for his research into the control and regulation of cell division and sexual reproduction in fungi. One of the advantages to Neurospora as a model organism is that it undergoes both sexual and asexual reproduction.

• Working with associates, Perkins identified many of the genes that control meiotic cell division in Neurospora crassa. In the process, he made fundamental discoveries about the cellular regulation and control of meosis.
• Building on his discoveries about meiosis, Perkins carried out investigations into ascospore genesis. Ascospore genesis, a form of sexual reproduction common to many fungi, has parallels with oogenesis and spermatogenesis in mammals and other chordates. Many of his papers in this area were concerned with genetic recombination, with the rearrangement of genes on paired chromosomes that occurs during reproduction, a phenomenon known as crossing over. Perkins developed techniques for mapping genes and centromeres on chromosomes based on the occasional errors, such as duplications and translocations, that occur in recombination.
• He trained many scientists to work with Neurospora crassa, and wrote several papers on working with, caring for, and maintaining Neurospora under laboratory conditions. He was instrumental in establishing and supporting the Fungal Genetics Stock Center. In 1968, he began a project to obtain wild type Neurospora at tropical and subtropical sites throughout the world. Perkins and his associates surveyed and collected more than 5,000 specimens of Neurospora and other fungi growing in the wild. Later, he initiated work on what would eventually become a worldwide resource for geneticists, The Neurospora Compendium: Chromosomal Loci. Published most recently in 2001, it serves as a reference for mutations and their loci in the Neurospora genome.

• Perkins, D; Davis, R (Dec 2000), "Evidence for Safety of Neurospora Species for Academic and Commercial Uses", Applied and Environmental Microbiology, vol. 66, no. 12, pp. 5107–9, Bibcode:2000ApEnM..66.5107P, doi:10.1128/aem.66.12.5107-5109.2000, PMC 92429, PMID 11097875
• The Perkins Lab — Neurospora genetics and biology Archived 2012-10-09 at the Wayback Machine
• David D. Perkins, Alan Radford, Matthew S. Sachs. The Neurospora Compendium: Chromosomal Loci. Academic Press: 1st edition (January 15, 2001). ISBN 0-12-550751-8.
• Rowland H. Davis: Neurospora. Contributions of a Model Organism. Oxford University Press, Oxford, 2000. ISBN 0-19-512236-4.

• David Perkins (geneticist) — Biographical Memoirs of the National Academy of Sciences