Saud al Faisal, 40 years representing the conservative Islamic kingdom was replaced wtih Adel al-Jubeir, the kingdom’s current ambassador to the US. . His departure comes as the world's top oil exporter attempts to navigate regional turmoil caused by the 2011 "Arab Spring", set against the backdrop of an overarching rivalry with Iran and bumps in its alliance with Washington.
Although foreign policy in the monarchy is ultimately determined by the king, Prince Saud has played an important role in shaping the country's response to the many crises affecting the Middle East.
His successor, former Washington ambassador Adel al-Jubeir, will inherit a heavy workload that has represented situation normal for a Saudi foreign minister since Prince Saud was appointed in October 1975.
His tenure included Israeli invasions of Lebanon in 1978, 1982 and 2006, the Palestinian intifadas that erupted in 1987 and 2000, Iraq invading Iran in 1980 and Kuwait in 1990, and a U.S.-led coalition's occupation of Iraq in 2003.
Despite the tumult of that history, he leaves the Arab world in a more parlous state than at any point in recent decades, with civil war in Syria and Iraq, chaos in Yemen and Libya and an uncertain political transition in Egypt.
Equally at home in Arab robes or tweed suit and tie and as fluent in English as in Arabic, Prince Saud has proved adept at cutting through flowery diplomatic niceties to deliver Saudi Arabia's message with pith and wit.
During a moment of tension in Saudi ties with its main ally the United States in 2004, he described the relationship as "a Muslim marriage" in which the kingdom could retain different wives if it treated them all with fairness.
Even in recent years, when a chronic back complaint and other maladies have made his hands appear shaky and his speech slurred during public appearances, he retained a knack for mental acuity.
Tentatively asked in early 2012 if he thought it was a good idea to arm Syria's rebels, he briskly retorted: "I think it's an excellent idea."
Prince Saud, a son of King Faisal, was born in 1940 in the mountain city of Taif near Mecca where, in 1989, he helped Saudi Arabia negotiate the agreement that ended Lebanon's 15-year civil war.
A degree at Princeton in the 1960s was followed by years at the Petroleum Ministry, where he was taken under the wing of his father's political alter ego, the canny and charismatic oil minister Ahmed Zaki Yamani.
His career as a diplomat began with trauma: the new King Khaled named him as foreign minister because of the assassination of Prince Saud's father Faisal, who had retained the foreign affairs portfolio after being made king in 1962.
For all his talents as a diplomat, however, Prince Saud has failed to build the kingdom's foreign ministry into a body with great institutional depth.
Diplomats in Riyadh have said Saudi foreign policy is like a searchlight: capable of intense focus only on the one area where the king and Prince Saud were most interested, but unable to follow up when attention shifted elsewhere.
When he was appointed in March 1975, the region was dominated by Cold War rivalries and secular, pan-Arab nationalism seemed to carry the promise of the future.
Egypt and Israel had not yet made peace, Yasser Arafat led the Palestine Liberation Organisation from shell-pocked refugee camps in Lebanon, Iran's shah ruled from his Peacock Throne and, in Iraq, a young Saddam Hussein was plotting his path to power.
Riyadh's relationship with Saddam, which went from wary support during the Iran-Iraq war to fierce enmity after the invasion of Kuwait, dominated long periods of Saudi foreign policy during Prince Saud's tenure.
However, despite that complicated history, Prince Saud publicly argued against the U.S.-led invasion of Iraq in 2003, presciently fearing a chaotic aftermath that could destabilise the region.
"If change of regime comes with the destruction of Iraq, then you are solving one problem and creating five more problems," he said in a British television interview.
In a sprawling ruling clan prone to clique-building, Prince Saud proved one of the closest allies of the late King Abdullah.
When Abdullah, then crown prince, embarked on his trademark set of economic reforms in 2000, it was Prince Saud, drawing on his oil ministry experience, who worked with him to offer foreign energy firms access to Saudi gas fields.
Two years later, he pushed Abdullah's biggest foreign policy initiative, an Arab plan for peace with Israel in return for a withdrawal from all occupied land and a resolution of the refugee problem, with similar gusto.
"All the neighbourhood, if you will, will be at peace with Israel, will recognise their right to exist. If this doesn't provide security of Israel, I assure you the muzzle of a gun is not going to provide that security," he said at the time.
Israel never agreed to the plan and Prince Saud has frequently spoken of the failure to help create a Palestinian state as the biggest disappointment of his career.