Upon completing her Ph.D. in 1996, Krylov joined the group of Prof. Martin Head-Gordon at the University of California, Berkeley, as a postdoctoral research associate, where she became involved with electronic structure method development.

Professor Krylov leads the iOpenShell lab,[4] a research group focused on theoretical modeling of open-shell and electronically excited species.

She develops robust black-box methods to describe complicated multi-configurational wave functions in single-reference formalisms, such as coupled-cluster and equation-of-motion (or linear response) approaches.

[7] In addition, Krylov develops many-body theories for describing metastable electronic states (resonances) and tools for spectroscopy modeling, including non-linear optical properties and core-level transitions.

Using the tools of computational chemistry, and in collaboration with numerous experimental laboratories, Krylov also investigates the role that radicals and electronically excited species play in such diverse areas as combustion, gas- and condensed-phase chemistry, astrochemistry, solar energy, quantum information storage, bioimaging, and light-induced biological processes.

Krylov has developed educational materials (computational labs and tutorials[10][11]) aiming to increase quantum chemistry literacy among chemists.

In 2015, Krylov delivered a public lecture in the Telluride Science Research Center Town Talk series entitled “Molecules and Light: The Story of Life, Death, and our Quest for Knowledge”.

In 2019 she received the American Physical Association's prestigious Earle K. Plyler Prize for Molecular Spectroscopy & Dynamics for her:"innovative work developing high accuracy electronic structure theory to inspire interpretation of spectroscopy of radicals, excited states, and ionization resonances in small molecules, biomolecules, and condensed phase solutes.

The award recognized her efforts to inform the scientific community and the general public through writings and speaking engagements of "the growing influence of politics and moral trends within STEM fields.

Her paper, "The Peril of Politicizing Science,"[33] which "launched a national conversation among scientists and the general public"[19] on the growing influence of political ideology over STEM, has received over 100,000 views and, according to Altmetric, was the all-time highest-ranked article in the Journal of Physical Chemistry Letters.