In the first such meeting between Syria and Israel at such a high level, Mr al-Sharaa was speaking at the White House before beginning talks with the Israeli Prime Minister, Ehud Barak. While setting a sober tone, the Foreign Minister said the Middle East was approaching a "moment of truth".
The stakes are also high for US President Bill Clinton, who is attempting to forge a legacy of fostering international peace, notably in the Middle East and in Northern Ireland. A settlement between Syria and Israel, ending more than half a century of aggression between them, would be a monumental prize.
Mr Clinton said as he stood between Mr Barak and Mr al-Sharaa in the White House rose garden: "What we are witnessing today is not yet peace and getting there will require bold thinking and hard choices.
"But today is a big step along that path. For the first time in history there is a chance for a comprehensive peace between Israel and Syria."
The two days of talks are not expected to produce any final agreements. It is more likely that they will kick off a longer process of negotiating that may take weeks or months. Joe Lockhart, President Clinton's spokesman, said: "I don't know that we can completely predict how that will play out."
At the heart will be Syria's demand for the return of the strategically important Golan Heights, seized by Israel during the 1967 Middle East war.
Mr Barak said that Israel was ready "to do whatever it takes" to reach a peace with Syria and "bring about the dreams of children and mothers" in the whole region. Before departing for Washington, Mr Barak warned Israelis to be ready for a "painful" outcome from the talks.
The Golan plateau is home to about 17,000 Jews who would have to leave before a handover.
In Washington, there were no affectations of great friendship on the lawn and no handshakes between the two sides for photographers.
"It goes without saying," Mr al-Sharaa said, "that peace for Syria means the return of all its occupied land, while for Israel, peace will mean the end of the psychological fear which the Israelis have been living in as a result of the existence of occupation."