Both houses of Congress voted in quick succession on Wednesday to approve the agreement, as well as pacts with Panama and Colombia.
It will now go to President Barack Obama to be signed into law.
The agreement is expected to increase US exports to the Asian economy by as much as $10bn (Â£6.5bn).
The free-trade deal with South Korea is the largest US trade pact since it signed the North American Free Trade Agreement in 1994.
However, it still needs to be passed by the South Korean parliament.
'Made in America'
President Obama said the pacts with South Korea, Panama and Colombia were "a major win for American workers and businesses".
"Tonight's vote, with bipartisan support, will significantly boost exports that bear the proud label 'Made in America', support tens of thousands of good-paying American jobs and protect labour rights, the environment and intellectual property," he said in a statement.
The Obama administration says that pact alone will support 70,000 American jobs.
There was nearly $80bn in trade between the US and South Korea last year. The Asian country is the seventh largest trade partner for the US.
The vote coincided with South Korean President Lee Myung-bak's arrival in Washington for an official visit.
In a speech on Wednesday he said the agreement would "send a powerful message to the world that the US and South Korea stand together in rejecting protectionism and that we are open to free and fair trade".
The pact was first agreed in 2007, but concerns in the US over tariffs imposed by South Korea on US carmakers delayed the proceedings.
US lawmakers have approved a long-delayed free trade agreement with South Korea, calling it the most significant in 16 years.