At an early stage in the development of the Mirage, consideration was given to a multi-role version placing emphasis on strike capability, this eventually materialising as the Mirage IIIE, of which the first of three prototypes flew on 5 April 1961. The airframe differed essentially from that of the Mirage IIIC in having an 30cm extension of the forward fuselage to permit enlargement of the avionics bay behind the cockpit. Dual-role radar was introduced and the Atar 09C-3 engine was adopted, this providing an afterburning thrust of 6200kg and being augmented by the 1500kg thrust of a SEPR 841 rocket motor.

The first production Mirage IIIE was delivered on 14 January 1964, and a total of 192 was subsequently delivered to France's Armee de l'Air. Built-in armament comprised two 30mm-cannon and maximum external ordnance load (distributed between five hardpoints) was 4400kg.

Versions were licence-built in Australia and Switzerland as the Mirage IIIO and IIIS respectively. Differences between the IIIE and IIIO were largely confined to avionics, and two versions were delivered to the RAAF, the IIIO(F) primarily for the intercept role, and the IIIO(A) for the attack task. Dassault supplied two pattern IIIO(F) aircraft, the first of which flew on 14 March 1963, and 48 IIIO(F) and 50 IIIO(A) Mirages were built for the RAAF by the Government Aircraft Factory and Commonwealth Aircraft. All IIIO(F) aircraft were converted to IIIO(A) configuration 1967-79 and the latter were finally withdrawn from service in 1988, the 50 surviving examples being procured by Pakistan in 1990. After acquiring a single Mirage IIIC for trials, Switzerland built 36 Mirage IIIS interceptors (plus 18 IIIRS reconnaissance aircraft), these entering service in 1966 with the Flugwaffe, and, in the early 'nineties, the 30 surviving IIIS fighters were being rotated through an upgrade programme (including the provision of canards) at Emmen.

Exports by the parent company were as follows: Argentina (17 IIIEAs), Brazil (20 IIIEBRs), Lebanon (10 IIIELs), Pakistan (18 IIIEPs), South Africa (17 IIIEZs), Spain (24 IIIEEs) and Venezuela (10 IIIEVs). The Brazilian IIIEBRs, ordered in 1970, were upgraded with canards, pressure refuelling, etc, from 1989, and the total quoted includes four ex-Armee de l'Air delivered in 1988 in the upgraded configuration. The South African IIIEZs were rebuilt to Cheetah EZ standard by Atlas Aircraft. In 1989, Dassault Aviation offered an upgrade of ex-Armee de l'Air aircraft as the Mirage IIIEX, this having canards, flight refuelling capability and a lengthened nose.