Helena Dalli has resigned as minister after Prime Minister Joseph Muscat nominated her to be Malta’s next European Commission member.
She is Malta's first-ever female nominee to the European Commission.
The Equality and European Affairs Minister will be replaced in cabinet by MP Edward Zammit Lewis, who served as Tourism Minister in the previous legislature and has led parliament’s Foreign and European Affairs Committee.
Dr Dalli will now focus on preparing for her grilling before MEPs as part of the nomination process, Dr Muscat said in a series of tweets announcing the change.
She will continue to serve as an MP "until her eventual confirmation", the government said in a statement.
The Prime Minister said he decided to nominate Dr Dalli after discussing the profiles of "two highly qualified individuals with [European Commission] President-Elect Ursula Von Der Leyen".
He did not identify the other individual considered for the nomination.
Ms Von der Leyen, who was approved as the European Commission's next president earlier this month, has emphasised her desire to ensure more gender balance within the Commission.
Talk of the town
Rumours surrounding Dr Dalli's nomination have been swirling for months, with some reports even suggesting she had been taking French lessons in preparation for her new role in Brussels.
Reports also suggested Dr Muscat was considering Finance Minister Edward Scicluna as a potential nominee.
Dr Muscat also thanked current EU commissioner Karmenu Vella for his work, saying Mr Vella led a "global campaign against plastic marine pollution, among others".
In a tweet, Commissioner Vella also thanked Dr Muscat for the trust placed in him five years ago.
He said it was an honour and a privilege to have had the chance to represent the EU on the environment, maritime affairs and fisheries.
Dr Zammit Lewis, who will replace Dr Dalli as a cabinet minister, said he would look to build on her "unprecedented achievements".
As Equality Minister, Dr Dalli oversaw the introduction of laws which introduced marriage equality and outlawed gay conversion therapies, as well as legislation granting wide-ranging legal recognition to transgender and intersex individuals.
The International Lesbian, Gay, Bisexual, Trans and Intersex Association currently lists Malta as the country with the most gay-friendly laws in the world.
The European Commission is made up of one person from each member state. Under EU rules, states' nominees must undergo a parliamentary vetting process prior to assuming their post.
That tough process sees nominees grilled by MEPs who sit on committees related to the nominee's prospective portfolio.
After MEPs question nominees, the full Commission, including the Commission President and the High Representative for Foreign Affairs and Security Policy, needs to be approved in a single vote of consent by parliament.