"The Iraqi nation should courageously resist the US security pact just as they have so far resisted the occupiers," Larijani said in a speech in the religious city of Qom on Thursday.
"The occupiers' withdrawal is the only way to implementing security in Iraq," he said, describing the military agreement as a "challenge threatening the Iraqi people and government."
Washington and Baghdad are negotiating a Status of Forces Agreement aimed at giving a legal basis to American troops in Iraq after December 31, when a UN mandate defining the current status of foreign forces expires.
The proposed pact has come under fire from religious and political leaders in Iraq.
Iran strongly opposes the US military presence in its neighbour to the west, and has been repeatedly accused by Washington of arming and training Shiite militias in Iraq.
Tehran denies the allegations and says it backs the Shiite-led Baghdad government of Prime Minister Nuri al-Maliki.
