The royal couple lived on the island as newlyweds before the Queen's accession to the throne, and celebrated their 60th wedding anniversary there in 2007.
The monarch will open the Commonwealth Heads of Government Meeting (Chogm) in the capital Valletta during the visit.
British High Commissioner to Malta Rob Luke said the Royal Family had an "enduring affection" for Malta.
The Queen and duke will be greeted by Malta's Prime Minister Joseph Muscat at the airport and will then receive a ceremonial welcome, attended by President Marie-Louise Coleiro Preca, in Valletta.
The couple will be meeting some former associates from the time they spent on the island, from 1949 to 1951, during the visit.
The Queen will also be accompanied by the Prince of Wales and Duchess of Cornwall on the tour.
It will be the fourth time Charles, who is due to make a speech on climate change at a business forum, has attended Chogm.
The monarch will open the event on Friday with a speech to the Commonwealth leaders and attend a banquet that evening.
UK Prime Minister David Cameron and Foreign Secretary Philip Hammond are expected to attend the meeting.
Mr Cameron wants discussions to focus on ways Commonwealth countries can work together to defeat terrorist groups.
Source: BBC News