The amendment, tacked on to a sweeping defense spending bill being debated by the chamber, passed 94-0 and should sail through the House of Representatives.
It was introduced by Senator Robert Menendez out of concern that Iran was pressing ahead with its nuclear weapons drive despite earlier sanctions that had been hailed as the toughest-ever against the Islamic republic.
"Yes, our sanctions are having a significant impact, but Iran continues their work to develop nuclear weapons," said Menendez, a Democrat.
He cited last week's report by the International Atomic Energy Agency that Iran continues to defy the United Nations and world community by refusing to slow uranium enrichment, denying access to inspectors and conducting live tests of conventional explosives that could be used to detonate a nuclear weapon.
"By passing these additional measures ending sales to and transactions with Iranian sectors that support proliferation -- energy, shipping, ship-building and port sectors as well as with anyone on our specially designed national list -- we will send a message to Iran that they can't just try to wait us out."
Building on the sanctions passed last year, the amendment would designate Iran's energy, port, shipping and ship-building sectors as "entities of proliferation" because they "support and fund Iran's proliferation activities."
Under the new rules, the United States would sanction anyone selling or supplying certain commodities to Iran -- including graphite, aluminum, steel, and some industrial software -- that are relevant to the country's ship-building and nuclear sectors.
Despite tough US and European sanctions, Tehran has been able to bypass certain restrictions by accepting payment in forms like gold for certain exports.
The Menendez amendment targets such circumventions by seeking to prevent Iran's central bank from receiving payment in precious metals.
The sanctions would also designate the Islamic Republic of Iran Broadcasting and its president as "human rights abusers" for airing forced televised confessions and show trials.
Senator John McCain offered his blunt assessment of the need for expanded sanctions to counter Iran's intentions.
"The screws need to be tightened," the Republican said on the Senate floor before the vote. "The centrifuges are still spinning in Tehran."
McCain said the new sanctions "can -- I emphasize can -- lead to a way to prevent a conflagration in the Middle East."
The far-reaching defense spending bill, when it passes, would have to be reconciled with the House version passed in July, but the sanctions amendment is safe, as the Republican-led House has been highly supportive of previous Menendez sanctions legislation against Iran.