Following S.H.I.E.L.D.'s delegitimization due to the Cambridge Incident, the conflict between HYDRA and S.H.I.E.L.D. led to numerous battles, some of them taking place in Washington, D.C. like the Massacre at the S.H.I.E.L.D. Academy, during which countless S.H.I.E.L.D. agents like Jemma Simmons were killed. While achieving its world domination, HYDRA settled its headquarters in Washington, D.C., at the Triskelion. In their hunt of Inhumans, HYDRA put in place several controls on the roads leading to Washington, D.C. The city was also patrolled by drones.
After plugging herself to the Framework, Jemma Simmons found Phil Coulson at the Alexander Pierce High School but he reported her as a subversive to HYDRA, leading to a hot pursuit within the city.
Following the capture of Agent Antoine Triplett, S.H.I.E.L.D. intercepted a HYDRA bus they later used to infiltrate the HYDRA Enlightenment Cultivation Center, which was partly destroyed in the ensuing fight between S.H.I.E.L.D. and HYDRA, killing the Patriot.
Daisy Johnson and Melinda May performed a spectacular evasion from the Triskelion, severely wounding Madame Hydra in the process. This resulted in a massive increase of HYDRA patrols in the street. A gunfight erupted near a S.H.I.E.L.D. safehouse, but the fugitives eventually escaped and made it to the Playground.
In an attempt to undermine HYDRA's domination, S.H.I.E.L.D. stormed the HYDRA Broadcasting Center and broadcasted a subversive video message featuring Coulson. The operation proved to be successful and protests against HYDRA began to rise, including in Washington, D.C. The Triskelion was later attacked by rebels against HYDRA and Yo-Yo Rodriguez only made it thanks to Holden Radcliffe, who brought her to the Playground.
When Aida initiated the destruction of the Framework, many elements of the city, from simple objects to elements of landscape, began to randomly vanished. Alphonso Mackenzie and Burrows tried to evacuate all the refugees sheltered at the Playground, hoping to escape the phenomenon, but to no avail. Eventually, the whole city and its inhabitants were permanently deleted.
- Agents of S.H.I.E.L.D.