Mrs Palin said in a statement that the decision came after much thought, and that she and her husband, Todd, "devote ourselves to God, family and country".
The 47-year-old's announcement ends months of uncertainty over her plans.
Ex-Massachusetts Governor Mitt Romney and Texas Governor Rick Perry lead the Republican pack to challenge Barack Obama for the White House in 2012.
"After much prayer and serious consideration, I have decided that I will not be seeking the 2012 GOP nomination for President of the United States," Ms Palin wrote in a letter to supporters.
"My family comes first and obviously Todd and I put great consideration into family life before making this decision."
Continue reading the main story Steve Kingstone BBC News, WashingtonIt's not a big surprise. For months the polls have shown a distinct lack of support among Republican voters for a Palin presidential bid.
And while party movers and shakers were shrieking for New Jersey Governor Chris Christie to enter the race, there was a deafening silence regarding Mrs Palin.
The GOP faces searching questions about 2012 but the former Alaska governor was simply not the answer.
That's not to say that Sarah Palin cannot play a part in the campaign. Last year's midterms showed her to be a fiery, formidable campaigner for Republican congressional and gubernatorial candidates, a role she will now reprise with gusto.
Likewise, the declared Republican candidates for the presidency will compete for her blessing and for the support of her loyal followers.
The decision draws a line under the existing Republican field. It now looks to be a case of the centrist former Massachusetts Governor Mitt Romney versus whichever of the more conservative candidates can challenge him. Texas Governor Rick Perry, in particular, will be breathing a sigh of relief because a Palin run might have further eaten into his already shrinking support.
But Mrs Palin said that in the coming weeks she would "co-ordinate strategies to assist in replacing the president, re-taking the Senate, and maintaining the House".Mrs Palin did not endorse any of the existing presidential contenders, but ruled out running as a third-party candidate.
Speaking to talk radio host Mark Levin, she said: "I would assume that a third party would just guarantee Obama's re-election and that's the last thing our republic can afford. So the consideration is not there for a third party, no."
Her announcement comes a day after New Jersey Governor Chris Christie ruled himself out of the race.
Mrs Palin burst on to the national political scene in 2008 as the vice-presidential candidate on the White House ticket of Arizona Senator John McCain.
After losing the 2008 election she returned to Alaska, and then stepped down as governor half way through her first term.
Mrs Palin had fanned speculation that she was considering a bid for the presidency when she announced a summer bus tour with stops in early-voting US states.
She has been a champion of the conservative Tea Party movement and is one of the most recognisable faces in US politics.
The mother-of-five has signed a number of lucrative television deals, published two best-selling books and set up a successful fundraising machine.