[2] Prior to her role at Microsoft, Brill was nominated by President Barack Obama on November 16, 2009, and confirmed unanimously by the US Senate to serve as Commissioner of the US Federal Trade Commission on March 3, 2010.

[14] In 2009, President Barack Obama nominated Brill to replace Pamela Jones Harbour as a member of the Federal Trade Commission (FTC).

[16][17] While at the FTC, Brill focused on the privacy implications of emerging technologies, including how personal data is gathered and used.

[21] In 2014 she appeared on CBS 60 Minutes to discuss the data broker industry and what needs to change to provide more control for consumers.

[23] She also dissented from the Commission’s decision to allow two Pharmacy Benefit Manager companies to merge because the merger would likely increase the cost of healthcare, an issue that the FTC began to investigate in 2023.

In this role, she leads the company's work in privacy, digital safety, regulatory governance, law enforcement and national security, telecom, standards, and accessibility regulation.