The National Highway Traffic Safety Administration (NHTSA) said it was acting following 11 Tesla crashes since 2018 involving emergency vehicles.
In some cases, the Tesla vehicles "crashed directly into the vehicles of first responders", it said.
The investigation will cover roughly 765,000 Tesla cars made since 2014.
That includes those in the Model Y, Model X, Model S and Model 3, the NHTSA said - the entire current range.
The agency was primarily concerned with an apparent inability of Tesla vehicles to cope with vehicles stopped in the road - specifically emergency vehicles attending an incident.
Among the list of cases was one where a Tesla "ploughed into the rear" of a parked fire engine attending an accident, and another in which a parked police car was struck.
The NHTSA said it was opening its preliminary investigation into "the technologies and methods used to monitor, assist, and enforce the driver's engagement", while using Autopilot.
It said that in the 11 crashes that prompted its investigation, either Autopilot or a system called Traffic Aware Cruise Control had been active "just prior" to the collisions.