The definitive attack version of the Intruder, introduced in 1970, with its first deployment 9 December 1971, with vastly upgraded nav/attack systems. The original search and track radars of the A-6A were replaced by a single AN/APQ-148 Norden multi-mode radar, and the onboard computers with a more sophisticated (and generally more reliable) solid-state electronic system. A new AN/ASN-92 inertial navigation system was added, along with the CAINS (Carrier Aircraft Intertial Navigation System), for greater navigation accuracy. Beginning in 1979 all A-6Es were fitted with the AN/AAS-33 DRS (Detecting and Ranging Set), part of the TRAM (Target Recognition and Attack, Multi-Sensor) system, a small, gyroscopically stabilized turret, mounted under the nose of the aircraft, containing FLIR boresighted with a laser spot-tracker/designator. TRAM was matched with a new AN/APQ-156 Norden radar. The BN could use both TRAM imagery and radar data for extremely accurate attacks, or use the TRAM sensors alone to attack without using the Intruder's radar (which might warn the target). TRAM also allowed the Intruder to autonomously designate and drop laser-guided bombs. In addition, the Intruder used AMTI (Airborne Moving Target Indicator) which allowed the plane to track a moving target (such as a tank or truck) and drop ordnance on him even though the target was moving. Also, the computer system allowed the use of Offset Aim Point (OAP), giving the crew the ability to drop on a target unseen on radar by noting coordinates of a known target nearby and entering the offset range and bearing to the unseen target.

In the early 1990s some surviving A-6Es were upgraded under SWIP (Systems/Weapons Improvement Program) to enable them to use the latest precision-guided munitions, including AGM-65 Maverick, AGM-84 Harpoon, AGM-84E SLAM, AGM-62 Walleye and the AGM-88 HARM anti-radiation missile. After a series of wing-fatigue problems, about 85% of the fleet was fitted with new graphite/epoxy/titanium/aluminum composite wings.

A-6E models totaled 445 aircraft, about 240 of which were converted from earlier A-6A/B/C models.