Helen Zeese Papanikolas was born in 1917 in Cameron, Carbon County, Utah, to Greek immigrants Emily Papachristos and George Zeese, who established the Success Market chain in Salt Lake City, where the family moved in 1933. Editor of the campus literary magazine Pen, she received a B.A. degree from the University of Utah in 1939. She married Nick E. Papanikolas, and they have two children.

Her publication in 1954 of "The Greeks of Carbon County" signaled the beginning of an important new phase in the writing of Utah history that came to full fruition in the 1970s and 1980s with the publication of numerous works on ethnic history and folklore. Her studies and those of others stimulated by her pioneering work broadened the scope of Utah history, which had generally focused on settlement and progress under Mormon direction, and contributed to a fuller understanding of the state's industrial development and its rich cultural heritage. Major publications by Papanikolas include Toil and Rage in a New Land: The Greek Immigrants in Utah (1970), The Peoples of Utah (1976), and Emily-George (1987).

A leading authority on Greek immigrant life in the United States, she has presented papers at national and international conferences and has served as a consultant for television documentaries and other projects. The Peoples of Utah Institute, of which she was a founder (1977) and the first president, located and identified artifacts associated with ethnic life, produced a major museum exhibit, and sponsored lectures and other programs. Papanikolas also collected numerous documents, conducted extensive interviews, and was instrumental in organizing the ethnic archives at the University of Utah. Her influence on research into ethnic life in Utah is great and unparalleled.

She has received many awards, including Archbishop of the Americas Iakovos Saint Paul Medal (1972); Fellow of the Utah State Historical Society (1975); Japanese-American Citizens League Award (1976); Brotherhood Award, National Conference of Christians and Jews, Utah Chapter (1978); Distinguished Alumna Award, University of Utah (1983); and Honorary Doctor of Humane Letters, University of Utah (1984). She has served on the Children's Service Society Board (1962-69); Advisory Board of Editors, Utah Historical Quarterly (1969-73); Board of State History (1973-85); and Utah Endowment for the Humanities State Committee (1973-79).