While the Mirage IIIC was being put into production, Dassault was also considering a multi-role/strike variant of the aircraft, which eventually materialized as the Mirage IIIE. The first of three prototypes flew on 1 April 1961.

The Mirage IIIE differed from the IIIC interceptor most obviously in having a 300 mm (11.8 in) forward fuselage extension to increase the size of the avionics bay behind the cockpit. The stretch also helped increase fuel capacity, as the Mirage IIIC had marginal range and improvements were needed. The stretch was small and hard to notice, but the clue is that the bottom edge of the canopy on a Mirage IIIE ends directly above the top lip of the air intake, while on the IIIC it ends visibly back of the lip.

Many Mirage IIIE variants were also fitted with a Marconi continuous-wave Doppler navigation radar radome on the bottom of the fuselage, under the cockpit. However, while no IIICs had this feature, it was not universal on all variants of the IIIE. A similar inconsistent variation in Mirage fighter versions was the presence or absence of an HF antenna that was fitted as a forward extension to the vertical tailplane. On some Mirages, the leading edge of the tailplane was a straight line, while on those with the HF antenna the leading edge had a sloping extension forward. The extension appears to have been generally standard on production Mirage IIIAs and Mirage IIICs, but only appeared in some of the export versions of the Mirage IIIE.

The IIIE featured Thomson-CSF Cyrano II dual mode air / ground radar; a radar warning receiver (RWR) system with the antennas mounted in the vertical tailplane; and an Atar 09C engine, with a petal-style variable exhaust.

The first production Mirage IIIE was delivered to the AdA in January 1964, and a total of 192 were eventually delivered to that service. Total production of the Mirage IIIE, including exports, was substantially larger than that of the Mirage IIIC, including exports, totaling 523 aircraft. In the mid-1960s one Mirage IIIE was fitted with the improved SNECMA Atar 09K-6 turbojet for trials, and given the confusing designation ofMirage IIIC2.

The Mirage IIIEBR has been in service with Brazil since 1972 with the initial procurement of 12 Mirage IIIE single seat and 4 two seat Mirage IIID aircraft. In the 80s and 90s another 20 ex French AF aircraft were purchased as attrition replacements and to keep the fleet viable. In 1989 all Mirage IIIEBRs entered a limited upgrade program. The upgrade consisted of the installation of canards and some minor mechanical and structural modifications.

To replace the ageing MATRA R.530 air-to-air missile, of which only one could be carried on the centerline pylon, all aircraft were modified in 1997 to carry two Israeli Rafael Python III air-to-air missiles on their outboard wing pylon. The modification also allowed the Brazilian Mectron MAA-1 Piranha, and the AIM-9B Sidewinder missiles to be carried on the same stations under the wings. Completing the modifications, a chaff and flare dispenser system was also installed to improve the self-defense capabilities of the Mirage IIIEBR.  The type was finally withdrawn from service in 2005 as it was obvious that the aircraft was no longer a viable offensive asset.