Colorado voters passed Amendment 64, allowing for the legal, recreational use of marijuana, according to KUSA Political Analyst Floyd Ciruli.
Amendment 64 will allow adults over 21 years of age to possess up to an ounce of marijuana. It also would allow people to grow as many as six marijuana plants in private, secure areas.
Washington State voters also voted to legalize recreational use for marijuana.
Both measures set up a showdown with the federal government.
"The voters have spoken and we have to respect their will. This will be a complicated process, but we intend to follow through. That said, federal law still says marijuana is an illegal drug so don't break out the Cheetos or gold fish too quickly," Gov. John Hickenlooper said in a statement.
"The Department of Justice's enforcement of the Controlled Substances Act remains unchanged," Jeff Dorschner, spokesman of the U.S. Attorney's Office, said. "In enacting the Controlled Substances Act, Congress determined that marijuana is a Schedule I controlled substance. We are reviewing the ballot initiative and have no additional comment at this time."
More than 300 Colorado doctors offered their names in support of Amendment 64. However, the state's chapter of the American Academy of Pediatrics urged a "no" vote. Supporters say alcohol does far worse things than marijuana.
"We know that many Coloradans are ready to end the failed policy of marijuana prohibition," Campaign to Regulate Marijuana Like Alcohol spokesperson Betty Aldworth told 9NEWS in September. "We can create a system where marijuana is controlled. We will have an easier time keeping it out of the hands of children."
She cited a recent study by the Centers for Disease Control which suggests marijuana use among high-school students in Colorado dropped between 2009 and 2011 as evidence that medical-marijuana regulation is having an impact.
"In an unregulated, underground market there are no controls," Aldworth said.
"Tonight marks the end of this campaign, but only the beginning of a process through which Colorado will show the world what a properly regulated marijuana system looks like. It will serve as a model for other states and, in fact, the rest of the world. It is impossible to overstate the significance of this victory," Rob Kampia, executive director of the Marijuana Policy Project - the primary financial backer of Amendment 64 - said.
Voters rejected Amendment 44 in 2006.
That amendment would have legalized the possession of a small amount of marijuana, but did not include the regulatory framework that Amendment 64 possessed.
While the general election might not break partisan gridlock in Congress, it could result in historic changes for U.S. social policy: Several states had a chance to be the first to approve same-sex marriage by popular vote and to legalize recreational use of marijuana.