Dayhoff's husband was Edward S. Dayhoff, an experimental physicist who worked with magnetic resonance and with lasers. They had two daughters who are also academics, Ruth and Judith.
Judith Dayhoff has a Mathematical Biophysics PhD from University of Pennsylvania and is the author of Neural network architectures: An introduction and coauthor of Neural Networks and Pattern Recognition.
Ruth Dayhoff graduated summa cum laude in Mathematics from the University of Maryland and focused on Medical Informatics while doing her MD at Georgetown University School of Medicine. During medical school, she co-authored a paper and a chapter in The Atlas of Protein Sequence and Structure with her mother, describing a new way to measure how closely proteins are related. Her husband Vincent Brannigan is Professor Emeritus of Law and Technology at the University of Maryland School of Engineering. Ruth was a founding Fellow of the American College of Medical Informatics.  She pioneered the integration of Medical Imaging and invented the Vista Imaging System.  She was chosen for the National Library of Medicines project on the 200 women Physicians who "changed the face of medicine." She serves as director of Digital Imaging in Medicine for the United States Department of Veterans Affairs.