It has set up an initiative that will try to shut down the web stores and educate people about the dangers of buying drugs from such places.
Search firms, payment providers and net hosting firms have all pledged to help the crackdown.
Research suggests about 36 million Americans have bought medicines from unlicensed web pharmacies.
“Those who sell prescription drugs online without a valid prescription are operating illegally, undercutting the laws that were put in place to protect patients, and are thereby endangering the public health,” said Victoria Espinel, US intellectual property enforcement co-ordinator, in a statement.
“It is a real wake-up call that so many Americans have engaged in this dangerous behaviour,” she said.
Web firms joining the initiative include search giant Google, domain registration firm Network Solutions, hosting companies as well as payment processors Paypal, Visa and Mastercard.
Together, the firms hope to tackle every link in the chain that keeps unlicensed pharmacies operating by stopping them showing up in search results, taking their websites offline, delisting the domains they use and stopping payments reaching them.
Many spammers align with online pharmacies and direct those who click on links in junk mail to the pedlars of fake pills.
The commercial partners in the initiative will also share information with law enforcement agencies and fund public awareness campaigns of the dangers of buying drugs from unlicensed pharmacies.
“The abuse of prescription medications is one of the most troubling public health problems in our country today,” said Steve Pasierb, president of the non-profit Drugfree.org which runs education campaigns about drug abuse.
Drugfree and the Alliance for Safe Online Pharmacies are planning research to find out why one in six Americans have bought drugs from web pharmacies. They will also look into what they buy and try to uncover the reasons some people see the practice as risky and others do not.
The initiative was announced at a White House summit on intellectual property and is one result of a plan the Obama administration submitted to Congress in mid-2010 that committed to tackling counterfeit medicines.