It was originally built in 1923 as an Italian air force base called aeroporto militare di Mellaha.

A motor racing circuit was subsequently built around the airport and Mellaha Lake began hosting the popular Tripoli Grand Prix in 1933.

It was used by the 376th Bombardment Group (Heavy) of the 12th Air Force for Consolidated B-24 Liberator bomb missions into Italy and southern parts of Germany.

Of the combat aircraft, the US State Department estimated in 1983 that fifty percent remained in storage, including most of the MiG fighters and Tu-22 bombers.

The base was a primary target of the 1986 United States bombing of Libya (Operation "El Dorado Canyon"), launched against Libya due to missile attacks on US aircraft and Libyan involvement in terrorist attacks against US servicemen in Europe.

[5] At 2 a.m. on 16 April 1986, Okba Ben Nafi AB, various Libyan government buildings, and three alleged Libyan terrorist training camps were bombed by General Dynamics F-111 Aardvarks from the 48th Tactical Fighter Wing, flying from the United Kingdom, to Libya.

[10] On 21 August 2011, rebels launched an assault on Mitiga as part of a bid to battle loyalist forces in Tripoli, sustaining a number of casualties in the process.

[11] On 25 October 2011 Google Earth released multispectral imagery from GeoEye taken on 28 August 2011 which showed the airfield as well as the highly capable MiG-25 aircraft with no visible damage.

[12] During the 2019–20 Western Libya campaign, the airport, held by military units loyal to the Government of National Accord, was repeatedly targeted with airstrikes from the opposing Libyan National Army[13] in order to enforce a no-fly zone declared by the LNA several days prior.