The airport is 23 kilometres (14 mi) from the city centre. The airport has its own postcode—Melbourne Airport, Victoria (postcode 3045). This is adjacent to the suburb of Tullamarine.

The Melbourne—Sydney air route is the third most-travelled passenger air route in the world and the busiest in the Asia Pacific region. The airport features direct flights to destinations in all states and territories of Australia in addition to numerous destinations in Oceania, Asia, Africa, Europe and North America. Melbourne is the most common destination for the airports of five of Australia's seven capital cities.N1 Melbourne serves as a hub for Qantas (Main Hub) and Virgin Blue, while Jetstar Airways and Tiger Airways Australia utilise the airport as home base. Melbourne is the busiest airport for international export freight as of December 2008, while second busiest for import freight. Domestically, Melbourne serves as headquarters for Australian air Express and Toll Priority and handles more domestic freight than any other airport in the nation.

In 2003, Melbourne received the International Air Transport Association Eagle Award for service and two National Tourism Awards for tourism services. Skytrax, an airline consultancy company, classifies Melbourne as a four-star airport. The airport comprises four terminals: one international terminal, two domestic terminals and one budget domestic terminal.

Before the opening of Melbourne Airport, Melbourne's international airport was Essendon Airport. By the 1960s, Essendon's limitations as Melbourne's main airport had become apparent. Essendon Airport's facilities were insufficient to meet the increasing demand for air travel; the runways were too short to handle the then new jet airliners and the terminals failed to handle the increase in passengers. Due to the encroachment of the urban boundary, the airport had become surrounded by residential housing, meaning that expansion of Essendon Airport was not possible. In October 1964, Ansett Australia launched the Boeing 727, the first jet aircraft used for domestic air travel in Australia, placing further strain on Essendon and increasing the need for a new airport.

But advances had been made before the launch of the new jet aircraft in Australia. On 27 November 1962, Prime Minister Robert Menzies announced a five-year plan to provide Melbourne with a AU$45 million "jetport" by 1967. A site in Tullamarine was chosen, maintaining proximity to Essendon.

In line with the five-year plan, the airport was ready to handle aircraft by 1967, but not passenger flights. Air Force One landed at the airport on 22 December 1967, carrying United States President Lyndon B. Johnson. Prime Minister John Gorton officially opened the airport to international operations on 1 July 1970 to much fanfare. Essendon still was home to domestic flights for one year, until they were transferred to new airport on 26 June 1971, and the first arrival of a Boeing 747 occurred later that year. In the first year of operations, Melbourne handled six international airlines and 155,275 international passengers.

In 1988, the Australian Government formed the Federal Airports Corporation (FAC) and placed Melbourne Airport under operational control of the FAC along with 21 other airports around the nation. The domestic terminals were significantly upgraded in 1990, and an upgrade of the international terminals began in 1991. In April 1994, the Australian Government announced that all airports operated by Federal Airports Corporation would be privatised in several phases. The carparks were upgraded between 1995 and August 1997.

Melbourne Airport was privatised on 2 July 1997 when it was leased to the newly formed Australia Pacific Airports Corporation Limited. In July 1997, the Melbourne Airport website was launched, providing Australia's first real-time flight operations data over the internet. Since privatisation, further improvements to infrastructure have begun at the airport, including expansion of runways, car parks and terminals.

Melbourne Airport was originally called Tullamarine Airport, after the adjacent suburb of the same name. Tullamarine derives from the indigenous name Tullamareena. International has sporadically been used in the name of the airport. After privatisation, the name changed to Melbourne Airport, following the lead of most other major Australian airports. Locally, the airport is commonly referred to as Tullamarine or simply as Tulla to distinguish the airport from the other Melbourne airports: Avalon, Essendon and Moorabbin.

Melbourne Airport's terminals have 56 gates: 40 domestic and 16 international. There are six dedicated freighter parking positions on the Southern Freighter Apron. The current terminal numbering system was introduced in July 2005; they were previously known as Qantas Domestic, International, and South (formerly Ansett Domestic).