The F-16E/F is an F-16, but it is one unlike any other F-16 variant in the world. The aircraft is more of a redevelopment of sorts the F-16 than just another incremental upgrade. Originally, when the program spun up in the 1990s, with an order eventually being placed for 80 advanced F-16s in 1998, the aircraft was going to be an even more drastic redesign of the F-16.

The Block 60 was designed for the United Arab Emirates Air Force (UAEAF). Based on the F-16C/D Block 50/52, it features improved radar, avionics and conformal fuel tanks. At one time, this version was incorrectly thought to have been designated "F-16U". A major difference from previous blocks is the Northrop Grumman AN/APG-80 Active electronically scanned array (AESA) radar, which gives
the airplane the capability to simultaneously track and destroy ground and air threats. The Block 60's General Electric F110-GE-132 engine is a development of the −129 model and is rated at 32,500 lbf (144 kN). The Electronic Warfare system is supposed to be quite advanced and includes the Northrop Grumman Falcon Edge Integrated Electronic Warfare Suite RWR together with the AN/ALQ-165 Self-Protection Jammer. Falcon Edge, which was developed by Northrop Grumman specifically for the Block 60, is capable of showing not only the bearing of any threat but also the range.

The Block 60 allows the carriage of all Block 50/52-compatible weaponry as well as AIM-132 Advanced Short Range Air-to-Air Missile (ASRAAM) and the AGM-84E Standoff Land Attack Missile (SLAM). The CFTs provide an additional 450 US gallon (2,045 L) of fuel, allowing increased range or time on station. This has the added benefit of freeing up hardpoints for weapons that otherwise would have been occupied by underwing fuel tanks. The MIL-STD-1553 data bus is replaced by MIL-STD-1773 fiber-optic data bus which offers a 1,000 times increase in data-handling capability. UAE funded the entire $3 billion Block 60 development costs, and in exchange will receive royalties if any of the Block 60 aircraft are sold to other nations. According to press reports quoted by Flight International, this is "the first time the US has sold a better aircraft [F-16] overseas than its own forces fly". Like the F-35, the Block 60 F-16 has a built in FLIR/laser targeting system rather than using a dedicated pod that would occupy a hardpoint, increase drag and RCS.