[1] From 1986 to 1999, Locascio was a research biomedical engineer in the molecular spectroscopy and microfluidic methods group in the analytical chemistry division of the National Institute of Standards and Technology (NIST).

[5] While working at NIST, she was encouraged by her manager Willie E. May and mentor Richard Durst to pursue a doctoral degree.

[1][4] At the University of Maryland, Katherine S. Squibb and Bruce O. Fowler, the director of the toxicology program, supported Locascio's efforts to attend graduate school while also working at NIST.

[9] She worked at NIST for 31 years, rising from a research biomedical engineer to eventually leading the agency's material measurement laboratory.

[10] Locascio also served as the acting associate director for laboratory programs, the number two position at NIST, providing direction and operational guidance for NIST's lab research programs[10] across two campuses in Gaithersburg, Maryland, and Boulder, Colorado.

[10] Locascio has published 115 scientific papers and has received 12 patents in the fields of bioengineering and analytical chemistry.

[12] She was the first person to serve as the vice president for research of both the College Park and Baltimore campuses.

[14] On July 16, 2021, President Joe Biden nominated Locascio as the under secretary of commerce for standards and technology.

[16] In January 2025, she assumed the role of president and CEO of the American National Standards Institute (ANSI).