The Senate embarked on a foreign-policy collision course with the Reagan administration last night, voting 73 to 22 to reject a proposed $354 million arms sale to Saudi Arabia.

The vote marked the first time that the Senate has explicitly rejected a proposed arms sale, and the margin, if sustained, was large enough to override an almost certain veto of the resolution of disapproval by President Reagan.

The House is expected to vote on the resolution today, with opponents of the sale predicting final passage by close to the two-thirds majority needed to override a veto.

Passage of the disapproval resolution by both chambers had been expected, with the crucial battle ahead over the attempt to override the anticipated veto.

Asked at his Tokyo news conference about the defeat of the arms sale and reverses of some elements in his tax-revision program, Reagan joked, "Just wait until the old man gets home."

Opponents of the sale, led by Sen. Alan Cranston (D-Calif.), sought to muster as large a vote as possible last night to demonstrate their ability to win a bruising veto fight.

The 73 votes, six more than needed to override a veto, provided a larger margin than expected.

Cranston said later that opponents of the sale are "very secure" in their confidence that they can override a veto and predicted that few senators would reverse their positions for fear of political retaliation.

The proposed sale involves delivery to Saudi Arabia of Stinger antiaircraft, Sidewinder air-to-air and Harpoon antiship missiles. Reagan submitted the proposed sale to Congress April 8 and, under law, the sale would take place unless both chambers passed a resolution of disapproval within 30 days. Thursday is the deadline for Congress to act.

In the brief debate, opponents denounced Saudi Arabia for undermining the Middle East peace process, supporting the Palestine Liberation Organization and for condemning last month's U.S. air raid on Libya.

"We want to make it clear that it is not in the national security interests of the United States to sell advanced weapons to nations that consistently scorn U.S. interests," Cranston said.

Dismissing the administration argument that the Saudis need the missiles for protection against Iran, which appears to have the advantage in its 5 1/2-year war with Iraq, Cranston noted that the weapons are not due for delivery until at least 1989.

He said the United States gained little from its previous arms shipments to Saudi Arabia, adding: "Now is not the time to sell more weapons to an uncertain friend in the Middle East."

Arguing in favor, Foreign Relations Committee Chairman Richard G. Lugar (R-Ind.) warned that the United States faces "serious and possibly long-lasting damage" to its Mideast interests if it rebuffs the security needs of a traditionally friendly, pro-western Arab nation.

The Saudis will buy the missiles elsewhere, Lugar said, costing the U.S. economy jobs and millions of dollars and undercutting administration influence in the Middle East.

"It is essential to our regional policy that we maintain viable relations with friendly states," Lugar said. "We cannot do this by disengaging from the region or by blocking an arms sale that breaks no new ground."

Despite his opposition and that of Majority Leader Robert J. Dole (R-Kan.), the disapproval resolution rolled through the Senate easily. The margin was all the more surprising since Israel and the main pro-Israeli lobbying organization, the American Israel Public Affairs Committee, did not actively oppose the sale.

Congressional opposition to arms sales to Arab nations has forced withdrawal or postponement of some sales, most recently a major arms package for Jordan.

The outcome of the battle over the missile sale seems certain to have implications for administration strategy in thwarting any drive to block delivery of five Airborne Warning and Control System (AWACS) radar reconnaissance planes to Saudi Arabia.

Congressional opponents failed to halt the $3.2 billion AWACS sale when the administration agreed to sell the planes in 1981. To win necessary congressional backing, Reagan had to promise that before delivery the administration would certify that Saudi Arabia was making a "substantial contribution to the peace and stability" of the Middle East.

Opponents are trying to mount a drive to overturn the agreement on grounds that the Saudis have not met that test.

However, administration sources said yesterday that they tentatively plan to send notification of Saudi compliance with terms of the AWACS sale to Congress early next month so delivery of the first AWACS can be made about June 28.

AWACS planes have been based in Saudi Arabia but operated by joint U.S.-Saudi crews.