The two-seat fighter jet departed the facility and headed to Eglin Air Force Base (AFB) in Florida for testing.
The aircraft has the capability to launch hypersonic weapons up to 22ft-long and weighs up to 7,000lb.
It features a new electronic warfare (EW) system, advanced cockpit systems, and the latest mission systems and software capabilities.
F-15EX programme manager colonel Sean Dorey said: “This is a big moment for the airforce. With its large weapons capacity, digital backbone, and open architecture, the F-15EX will be a key element of our tactical fighter fleet and complement fifth-generation assets.
“In addition, it’s capable of carrying hypersonic weapons, giving it a niche role in future near-peer conflicts.”
The USAF has plans to procure 144 F-15EXs from Boeing to replace all F-15C/D.
A second F-15EX will be delivered to Eglin AFB by the end of next month while the other six under Lot 1 aircraft will be delivered to Eglin AFB in FY2023.
US Air Force Materiel Command junior commander-general Arnold Bunch said: “I commend the dedicated efforts of the entire team for bringing this platform online in record time and in the middle of a global pandemic.
“With its open mission systems architecture and weapons capacity, the F-15EX will provide an outstanding capability for our nation for years to come.”
In January, Boeing secured a licence from the US Government to provide F-15EX fighter aircraft to the Indian Air Force.