Comcast told CNBC that the ads will run only during late night. Senior director of communications for sales, Melissa Kennedy, said while Comcast guidelines currently prohibit ads for recreational marijuana, "We do accept ads that refer to marijuana for medicinal purposes in those states that have legalized medical marijuana."
She added that Comcast recently started accepting ads from companies that serve clinics and patients, such as MarijuanaDoctors.com. It's also accepting ads from "vendors that provide operational services to retail establishments authorized by a particular state to sell marijuana, e.g., an ad from a software solution provider."
(Read more: Legal pot like 'alcohol after Prohibition': O'Leary)
This seems to indicate that Comcast could eventually consider commercials in states like Colorado and Washington where recreational pot is legal—not from actual retailers, but from companies selling things like growing equipment. Kennedy said Comcast may "want to tweak the guidelines" and the company is "careful about the networks on which they air."
This historic move is being praised by legalization advocates, but it is not sitting well with the Drug Free America Foundation.
"There is no question that these ads will be seen by young people and will not only further diminish their perception of marijuana being harmful, the ads will also promote the use and easy accessibility of the drug," Executive Director Calvina Fay said in a statement.
(Read more: Ka-ching! Pot tax creates windfall for one county)
"The Federal Communications Commission needs to take immediate action to stop the television advertisement of a federal crime," Fay said. "Or are they going to bury their heads in the sand on this issue like our attorney general?"
As for MarijuanaDoctors.com, CEO Jason Draizin told The Verge, "Securing the airtime for our commercial on a major network was extremely difficult and at the same time, extremely satisfying. ... We recognize that the sale and use of marijuana is still considered very controversial and we are pleased that Comcast understands that there are legitimate businesses providing legitimate and legal services to people who have legitimate needs.
Disclosure: Comcast is the owner of NBCUniversal, the parent company of CNBC and CNBC.com.
—By CNBC's Jane Wells. Follow her on Twitter: @janewells