[11] On April 26, 2016, Defense Secretary Ash Carter announced that President Obama had nominated Goldfein to succeed General Mark Welsh as the 21st Chief of Staff of the Air Force.

[17] The aim of rapidly connecting all aircraft data and sensors to each other, as well as, to other military assets was a special focus of the subject as he led the service.

[20] In August 2017, Goldfein joined other members of the Joint Chiefs of Staff in condemning racism in the wake of the Unite the Right rally in Charlottesville, which was organized by an ex-Marine.

[26][27] In June 2020, Goldfein publicly denounced the murder of George Floyd in a memo, calling it a "national tragedy" and adding that Americans "should be outraged" at the brutality shown during the incident.

[28][29][30] He supported his senior enlisted advisor, Chief Kaleth O. Wright, who responded to Floyd's murder on social media.

[29][32] Goldfein's term as Air Force chief of staff ended on August 6, 2020, and he was succeeded by General Charles Q.

[38][37][36][39] Goldfein did not express any rancor over not being selected, stating that the president had "the absolute right and responsibility to pick the principal military adviser that he wants.

[42] In March 2023, Goldfein joined Shield Capital's National Security Advisory Board, alongside H. R. McMaster, Letitia Long, James G. Stavridis and Sean Stackley.