In July 2022, she was named the editor-in-chief of Guardian US, succeeding John Mulholland, and assumed her new position in the autumn of that year.

[2][3][4] She has also edited several books of investigative journalism, including Blackwater and Dirty Wars by Jeremy Scahill, and the essay collection Going Rouge: Sarah Palin, An American Nightmare.

In an open letter dated January 14, 2021, Poitras singled out Reed and First Look Media's CEO Michael Bloom for her firing.

[9] Nevertheless, Betsy Reed oversaw the initial reporting on Winner’s NSA leak, and when their lone source's identity was compromised Intercept management ordered an internal review of the newsroom's handling of Winner's restricted documents (regarding Russian interference in the 2016 United States elections).

Reed did not fade into the background while the internal inspection was underway, she instead took an active behind-the-scenes role in The Intercept's investigation, assigned staff who reported directly to her to gather facts, and, when the facts pointed to editorial failures, Reed removed the staff person from the investigation, according to Laura Poitras.