First was known for his contributions to animal genetics, and in particular for the development of systems of bovine embryo cloning, gene transfer, and in-vitro production of livestock embryos. His research helped to make major advances in the application of biotechnology to reproduction in farm animals possible, eliminating the need for brood cows in beef cattle breeding. His research focused on sperm and oocyte maturation, in vitro production of embryos, cloning of cattle, and methods for producing transgenic embryos.
Neal L. First received several awards. He received the Animal Science Morrison Award, the Upjohn Research Award, the Society for the Study of Reproduction Research Award, the National Association of Animal Breeders Research Award and the Von Humboldt Award. In 1996/7, he received the Wolf Prize in Agriculture "for his pioneering research in the reproductive biology of livestock". He was at the faculty of the University of Wisconsin–Madison when he received the prize.