From Los Angeles to New York, protesters gathered in several cities to condemn the passage of California's Proposition 8, which the state's citizens voted on during the November 4 presidential election.
The controversial ballot measure, sponsored by socially conservative opponents of gay marriage and paid for by religious groups, amended the state constitution to define marriage as a union between a man and a woman.
The proposition passed by a 52.5 to 47.5 percent margin and effectively quashed a California Supreme Court decision earlier this year which had legalized gay marriage in the state.
Several thousand protesters rallied in front of Los Angeles City Hall on Saturday, calling for Proposition 8 to be declared invalid.
Under blue skies and blazing sunshine, protesters waved banners bearing slogans such as "No More Mr Nice Gay" and "Land of the Free My Ass."
A small handful of anti-gay marriage activists faced off with protesters who brandished banners reading "Homo Sex is Sin" and "God Does Not Love You Just the Way You Are."
A similar protest took place in San Diego, where around 11,000 people demonstrated peacefully despite an attempt by anti-gay marriage activists to disrupt the march, police said. One man was arrested for attempting to incite violence before being released.
In San Francisco, activists marched along Market Street as speakers, including local officials, urged crowds not to give up their quest for equality.
Other protests took place in New York, Chicago, Denver, Seattle, Portland, and Boston.
"Today is a national tipping point," Marriage Equality USA spokeswoman Molly McKay said in a statement. "History will look back on this day as the day that the national LGBT community rose up and said 'We are not going back."'
Meanwhile a crowd estimated at between 1,000 and 2,000 demonstrated in Salt Lake City, Utah on Saturday, where the Mormon Church is headquartered.
The Church of Jesus Christ of Latter-day Saints, the official name of the Mormon Church, has angered gay marriage supporters after giving backing to Proposition 8.
The keynote speaker at Saturday's rally in Salt Lake City was Jeff Key, a former US Marine and Iraq War veteran who was discharged after coming out as gay.
"I'm so glad Salt Lake City has become ground zero," Key was quoted as saying by the Salt Lake Tribune.
Meanwhile diversity trainer Dominique Storni told the crowd the Mormon Church had "wakened our sleeping giant."
"We finally have a civil rights movement equal to that of the '50s and '60s," Storni was quoted as saying.