Hammes-Schiffer held positions on the faculty at the University of Notre Dame as Clare Boothe Luce Assistant Professor of Chemistry and Biochemistry (1995-2000) and at Pennsylvania State University (2000-2012).  In 2012 she joined the University of Illinois at Urbana-Champaign as Swanlund Professor of Chemistry, where she remained until 2017. Since then, she has led the Hammes-Schiffer Research Group at Yale University, where she was named John Gamble Kirkwood Professor of Chemistry in 2018, and Sterling Professor of Chemistry in 2021.  Starting January 2024, she will join the faculty at Princeton University. Hammes-Schiffer is an author or co-author on nearly 200 papers, and has given more than 200 invited talks.