Prime Minister Lee Hsien Loong left for Europe on Saturday to attend the third Nuclear Security Summit in The Hague and then to visit Luxembourg and the United Kingdom.
The summit is a follow-up to the first two meetings that were held in Washington in 2010 and in Seoul in 2012.
Leaders of 53 countries, including United States President Barack Obama and Chinese President Xi Jinping, are expected to attend the Hague meeting.
The aim of this year's gathering is to assess the progress made over the past four years on national and international measures to enhance nuclear security, and discuss additional moves that may be needed.
The summit was initiated by President Obama in 2009, when he underscored the dangers of nuclear terrorism and called on countries to work together to ensure the security of nuclear materials so that they do not fall into the wrong hands.
While Singapore is not a nuclear power, it was invited to take part in the summit from the outset because of its status as a global trade hub.
Nuclear safety and security may be high on the agenda but a planned meeting of the G-7 club at the margins will likely also make the headlines as world leaders focus on the situation in Ukraine, following Russia's annexation of Crimea this week.
On the second leg of his trip, Mr Lee will be making his first visit to Luxembourg and meet his counterpart Xavier Bettel.
In Britain, he will hold talks with Prime Minister David Cameron.
Mr Lee will discuss ways to strengthen Singapore's bilateral cooperation with the two countries, and seek their support for the European Union-Singapore Free Trade Agreement.
The EU is Singapore's third-largest trading partner, after China and Malaysia.
Britain is Singapore's second-largest investment destination, behind China and just ahead of Malaysia, at $43.7 billion at the end of 2012.
While in London, Mr Lee will meet corporate chieftains, deliver a speech at Chatham House and attend the Singapore Day celebrations. He will be accompanied by Mrs Lee and officials from several agencies. Deputy Prime Minister Teo Chee Hean and Ms Grace Fu, who is Second Minister for Foreign Affairs and for the Environment and Water Resources, will join the delegation in Britain.
A statement from the Prime Minister's Office said that DPM Teo will be Acting Prime Minister until March 25 and DPM Tharman Shanmugaratnam will act for the Prime Minister from March 26 to March 30.