"American credibility will be seriously impacted if this doesn't go through," Foreign Minister K. Shanmugam said of the trade accord, which is in jeopardy in Washington.
He highlighted how US officials have been stressing the importance of reaching such a deal for many years.
"You are either in, or you're out," he told a seminar organized by The Atlantic magazine.
The Republican-run House of Representatives on Friday delivered a stinging blow to President Barack Obama by refusing to give him fast-track powers to present Congress with a trade accord for an up or down vote, with no amendments.
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Obama wants to finalize terms with 11 other Pacific Rim countries on what would be the largest trade agreement ever, a massive pact which would include Japan but not China.
Shanmugam pointed out the deal would also cover the 10-nation ASEAN states, which includes Singapore, and whose economies he said were projected to grow to $4 trillion within the next five years.
"So that's a huge economy," the Singaporean minister said.
"In a sense the history of East Asia and the Asia-Pacific is being re-written through trade deals."
The Obama administration has long pushed a so-called "rebalance" towards the fast-growing Asian region.
And the US has already negotiated the Trans-Pacific Partnership (TPP) with so many countries, "how do you think people will view America as a reliable partner?" if the deal falls through, Shanmugam asked.
"How do you think people will take your word in the future when you say you're going to do something? ... How do you think you can be taken seriously if after having put so much of your prestige on this, you don't do it?"
Obama has urged the House to vote again "as soon as possible" so US businesses can "sell goods made in America to the rest of the world.