The shooting erupted in a rural area 185 kilometres west of Philadelphia, not far from the Maryland line, police say.
"We grieve for the loss of life of three precious souls who served this county, served this commonwealth, served this country," Pennsylvania Governor Josh Shapiro said.
"This kind of violence is not OK, we need to do better as a society," he continued.
York Hospital said it was treating two people in serious condition and had enhanced security protocols in place.
"The grief will be unbearable but we will bear it," Pennsylvania State Police Commissioner Christopher Paris told a news conference, who said the shooter is also dead.
"We will not rest until we conduct a full, fair and competent investigation into this matter."
Attorney General Pamela Bondi called the violence against police "a scourge on our society". She said federal agents were on the scene to support local officers.
"Please send prayers to the officers and those involved in the shooting in York County," Pennsylvania Lieutenant Governor Austin Davis said in a social media post.
Pennsylvania Attorney General Dave Sunday said he was also on the scene.
Sunday said on social media he urges "all residents to follow the instructions of local law enforcement" and he is "praying for all involved".
A local school district issued a shelter-in-place order, though it said schools and students were not involved in the shooting.
The order was lifted later in the afternoon. The district said in a statement authorities "advised us to hold students and staff in our buildings as a precaution while several area roads are closed".
The medical response unfolded on a rural road in south-central Pennsylvania that winds through an agricultural area with a barn and farm fields.
Police have not provided any details about who was involved in the shooting.
Officers were keeping people well back from the scene in the area's rolling farmland, with some 30 police vehicles blocking off roads bordered by a barn, a goat farm and soybean and corn fields.
"Pennsylvania State Police, Northern Regional Police and numerous emergency responders are at the scene. The York County Commissioners are monitoring the situation closely and praying for all those involved," the county said in a statement.
An officer in the area was killed in February, when a man armed with a pistol and zip ties entered a hospital's intensive care unit and took staff members hostage before a shootout that left both the suspect and an officer dead.
With Reuters
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