The single-seat F-15C crashed in the mountains of western Virginia on Wednesday morning.
Col. James Keefe of the 104th Fighter Wing of the Massachusetts Air National Guard said at a news conference in Westfield, Massachusetts, that the missing pilot is an experienced flyer. He said the plane was on its way to New Orleans to have a radar installed as part of routine maintenance.
Keefe said he had not received confirmation that anyone had reached the crash site.
Officials say the pilot reported an inflight emergency, then lost radio contact.
The jet was on a standard training exercise to receive a system upgrade and had no munition onboard, said Maj. Matthew Mutti, from Barnes Air National Guard Base. He didn't say where the jet was headed or release the pilot's name.
The pilot made a report of an inflight emergency, then lost radio contact, officials said.
"Information on this incident is developing rapidly, and we are not going to speculate on what occurred or the status of the pilot," Col James Keefe, 104th Fighter Wing Commander, said in a statement. "We are hopeful that the pilot is OK, and the pilot will be in our thoughts and prayers."
Witnesses reported an explosion-like noise just before 9 a.m., according to Augusta County dispatcher Becky Coyner.
"It's the loudest noise I've ever heard," 63-year-old Rebecca Shinaberry, who lives on a farm about two miles away, told The Associated Press. "(It) just shook the ground, and from my house we could just see a big plume of smoke."
Deerfield is about 135 miles northwest of Richmond.
F-15s are maneuverable tactical fighters that can reach speeds up to 1,875 mph, according to the Air Force website. The F-15C Eagle entered the Air Force inventory in 1979 and costs nearly $30 million, the website says. The Air Force has nearly 250 of them.