Ms Rice said the signing of the document was an extraordinary occasion, adding that the agreement would help Nato, Poland and the US respond to "the threats of the 21st Century".
Speaking during the signing ceremony at the presidential palace in Warsaw, she emphasised that the missile system was "defensive and aimed at no-one".
While Washington believes placing 10 interceptor missiles on a disused military base near Poland's Baltic Sea coast will protect much of Nato against possible long-range attacks, Warsaw sees threats much closer to home, says the BBC's Adam Easton in Warsaw.
That is why it demanded - in exchange for hosting the base - short-range Patriot missiles for its own air defences and a guarantee that the US will come to its assistance in the event of an attack, our correspondent adds.
The demands had delayed the deal's completion, but the conflict in Georgia gave the negotiations more impetus, says the BBC's Kim Ghattas, who is travelling with Ms Rice.
Both the US and Poland say the system is not aimed against Russia.
But the agreement has infuriated Moscow, our correspondent adds.
Russia's deputy chief of general staff, Gen Anatoly Nogovitsyn, said last week the plans for a missile base in Poland "could not go unpunished".
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