The scenario has been played out many times in films such as "Armageddon" and "Deep Impact," but NASA and FEMA want to make sure they're prepared for real.
The agencies will run a drill at the Planetary Defense Conference in Maryland Monday.
During the simulation, scientists have discovered that an asteroid is set to strike in 2027. They'll then have to work through determining what regions are most at risk and how to respond to the threat.
Organizers say the events help disaster management teams develop more effective ways to communicate with each other.
NASA has participated in six similar impact exercises so far.
You can watch the simulation and the conference live on NASA's website.