In an editorial, the prestige publication said marijuana laws disproportionately impact young black men and that addiction and dependence are "relatively minor problems" especially compared with alcohol and tobacco.
"It took 13 years for the United States to come to its senses and end Prohibition, 13 years in which people kept drinking, otherwise law-abiding citizens became criminals and crime syndicates arose and flourished," the newspaper said.
"It has been more than 40 years since Congress passed the current ban on marijuana, inflicting great harm on society just to prohibit a substance far less dangerous than alcohol. The federal government should repeal the ban on marijuana."
Noting that the editorial board reached its conclusion after much discussion, The Times described the social costs of marijuana laws as "vast."
Citing FBI figures showing there were 658,000 arrests for marijuana possession in 2012 -- far higher than for cocaine, heroin and their derivatives -- it said "the result is racist, falling disproportionately on young black men, ruining their lives and creating new generations of career criminals."
While advocating for a ban on marijuana sales to those under 21, the paper also said the "moderate use of marijuana does not appear to pose a risk for otherwise healthy adults."
The editorial, titled "Repeal Prohibition, Again," kicks off a series of stories about the issue and invites readers to weigh in.
The call comes just weeks after recreational pot sales began in Washington, making the western US state just the second after Colorado to allow people to buy marijuana with no medical requirement.
Also earlier this month, Governor Andrew Cuomo signed a bill making New York the 23rd state to legalize marijuana for medical use.