[7][8] Monaco attended Harvard University, graduating with a Bachelor of Arts, magna cum laude, in American history and literature in 1990.

She was a research coordinator for the United States Senate Committee on the Judiciary, where she worked on the Violence Against Women Act, from 1992 to 1994 under then-chairman Joe Biden.

[10] Monaco enrolled at the University of Chicago Law School, working as an intern in the White House Counsel's Office in 1996 before earning her Juris Doctor (J.D.)

[19][20] On July 1, 2011, Monaco took office as assistant attorney general for national security following her appointment by President Barack Obama, leading the Justice Department division which oversees major counterterrorism and espionage cases, as well as authorizes the use of FISA warrants.

[29] In this role, Monaco led U.S. policy to disrupt terrorist threats against the United States, including degrading Al-Qaeda and affiliates from Al-Qaeda in the Arabian Peninsula to Jabhat Fateh al-Sham, putting the Islamic State of Iraq and the Levant on a lasting path to defeat, and building partner capacity to prevent and disrupt terrorist threats.

[30] She also led initiatives to expand collaboration with the private sector to counter ISIL's messaging and abuse of online platforms while lifting up alternative narratives.

[34] On May 23, 2013, Daniel Klaidman, writing for the Daily Beast reported a White House official confirmed Monaco would handle "day-to-day responsibilities" for Guantanamo.

[36][37][38][39] Scholars at Lawfare interpreted Monaco's comment as a sign that the Obama presidency would ask the United States Congress to pass legislation enabling Guantanamo to remain open after U.S. involvement in the Afghan war ended.

[citation needed] In February 2016, the White House and Department of Defense presented a comprehensive plan to Congress to close the detention facility at Guantanamo Bay.

[51] During her time at O'Melveny & Myers, Monaco advised high-profile clients including ExxonMobil, Apple Inc., in addition to her alma mater, Harvard University.

[53] In April 2020, it was announced that Monaco would assist with vetting efforts for the selection of Joe Biden's running mate in the 2020 presidential election.

[59] A coalition of progressive groups wrote in opposition to her nomination, arguing that Monaco's professional ties with Apple, currently under investigation by the DOJ, constituted a conflict of interest.

[63] In a 2021 interview with the Associated Press, Monaco stated that cybersecurity matters, including combating ransomware software and other cybercrime, would be a priority of the DOJ.