She served as acting United States attorney for the Northern District of Ohio from 2021 to 2022.

[2] From January 2021 to February 2022, she served as the acting United States attorney, and in turn chief federal law enforcement officer for the Northern District of Ohio.

President Biden nominated Brennan to the seat vacated by Judge Dan Polster, who assumed senior status on January 31, 2021.

[5] During her confirmation hearing, Senator Ted Cruz questioned her over her support for Case Western Reserve University law professor Ayesha Bell Hardaway, who stepped down from her position on a team examining ways to improve the Cleveland Police Department after saying she thought there should be an "honest and frank conversation and reckoning with the violence and the harm that continues to be inflicted against Black communities through law enforcement.

[7][8] On January 3, 2022, her nomination was returned to the president under Rule XXXI, Paragraph 6 of the United States Senate;[9] she was renominated the same day.