The procedural vote to cut off debate on the amendment would be added to a broader Middle East security bill that is likely to come up for a final Senate vote next week.
The amendment has no real impact on policy but signifies the broad opposition even in Trump's own party to a rapid removal of US troops from Syria, which the president announced in December.
Still, the bill also includes an anti-boycott, divestment and sanctions (BDS) amendment that may prove difficult to pass in the Democratic-controlled House of Representatives.
If the bill passes the Senate, it would then go to the House for a vote. If the House passes the legislation, it would head to the White House, but Trump has already vowed to veto the bill.
In the case of a veto, the bill would return to the Senate where a two-thirds majority vote could override the veto.
Ahead of the preliminary vote, Republicans Senator Marco Rubio said Trump's planned withdrawal was a "bad idea".
"That announcement alone has undermined our credibility in the eyes of our allies," he added.
Trump has come under mounting pressure from both parties and the bureaucracy over a number of his foreign policy measures.
On Tuesday, the top US intelligence chief said the Islamic State (IS) group still has "thousands" of fighters that it could rebuild into a cohesive force in any vacuum left in the war-torn country.
The next day, Trump took issue with that challenge to his stance, calling his intelligence chiefs "extremely passive and naive," adding: "Perhaps Intelligence should go back to school!"