The billboard sits near Newport Boulevard and says, "I do not find in Christianity one redeeming feature. It is founded on fables and mythology."
The billboard quotes Thomas Jefferson, but the Jefferson Library said there's no evidence the president ever said it.
A group called Backyard Skeptics, which includes atheists, is behind the billboard.
"If it wasn't quoted from Thomas Jefferson, then obviously they should have done their research first before putting something up like that," said Costa Mesa resident Donna Way.
An anonymous donor with the group paid $4,000 for two billboards to be on display for two weeks.
"I realized after the billboard was put up that it was a misquotation. There is no historical documentation of that," said Bruce Gleason, the head of Backyard Skeptics.
Gleason said the billboard was meant to promote secular values and "that you can do good and be good without God in the group Backyard Skeptics."
But Gleason admits the inaccurate quote could hinder their message.
"The billboard hurts us, because there are other religious people who have said, 'Look at those atheists, they're misquoting Jefferson.' Well I take it upon myself to say, yes I made a mistake," said Gleason.
Gleason's group has gained attention in the past with other billboards across Orange County. Despite the mistake, he believes Jefferson would not mind.
"Jefferson wouldn't be upset if he saw the billboard. He'd probably say, 'Yea, I kind of agree with that,' because all the other quotations that he's had are in the same vein," said Gleason.
According to the Jefferson Library, the president was not a Christian, but a deist who believed in a hands-off creator.
Other residents said they don't like the billboard and can't wait for it to come down.
Gleason said they plan to replace the billboard with another secular one, but it could take more than a week.