A specialist in algebraic geometry and number theory at Freie Universität, Esnault has published more than one hundred scientific papers, which is exceptional in her discipline. In mathematical professional circles, she is widely quoted.

From 1990 to 2012 Esnault, who was born in France, taught and conducted research at the University of Duisburg-Essen, where her husband Eckart Viehweg also held a chair in mathematics until his death in 2010. During this period the two of them jointly published more than 20 major publications. In 2003 both of them were awarded the Leibniz Prize of the German Research Foundation, which is considered the most important research award in Germany.

Hélène Esnault is a member of the National Academy of Sciences Leopoldina and the Berlin-Brandenburg Academy of Sciences and Humanities as well as a member of the editorial board of numerous prestigious journals such as the Duke Mathematical Journal, Mathematische Annalen, and Astérisque. She has received numerous awards in France and abroad. She has been a professor of mathematics at Freie Universität since October 2012 and is the first Einstein Professor at the university.