At a rally in his hometown of Hope, Arkansas, Mr Huckabee used the phrase "hope to higher ground" as a motif.
The bass guitar-playing, foreign policy hawk has had a media career since losing the nomination in 2008.
He joins a crowded Republican field that includes three senators, a businesswoman and a neurosurgeon.
"Folks, it is a long way from a little brick rent house on Second Street in Hope, Arkansas to the White House," he said.
"Here in this small town called Hope, I was raised to believe that where a person started didn't mean that's where he had to stop. I always believed that a kid could go from Hope to higher ground."
After announcing his ambitions, the crowd erupted in cheers of "We want Mike!"
The former Southern Baptist minister acknowledged his pro-gun-ownership position, telling the audience about receiving a BB gun at the age of five.
He said the US Department of Education should be abolished, a position popular with conservatives who oppose recent national education reforms.
On immigration, he said the US borders should be secured, but was short on details.
And he reaffirmed his steadfast opposition to same-sex marriage.
Mike Huckabee is back.
Eight years ago he launched a surprisingly successful presidential bid, finishing second to Arizona Senator John McCain and winning the Iowa caucuses and seven other states.
Four years ago rumours abounded that Mr Huckabee was going to run again. Supporters and analysts watched and waited...  and waited. The former Arkansas governor, who had a well-paying job as a television and radio host, opted to sit out the campaign, despite some polls showing him leading the Republican field. He said his "heart says no".
Now, however, Mr Huckabee's heart is saying yes. He has quit his media commitments and is diving into the 2016 race. He'll meet a much more crowded field than would have faced him in 2012, however, both in the total number of candidates and in opponents who will compete with him for the evangelical voters who buoyed his 2008 campaign.
Mr Huckabee has a lot going for him - name recognition, a developed fundraising network and experience from his previous presidential campaign.
But given the strength of his Republican opponents - new, engaging and also well-funded - will that be enough?
Early in his speech, Mr Huckabee noted that he was the first male in his family to graduate from high school.
"My dad wasn't an educated man, but he was a smart man. And he and my mother didn't have a whole lot, but they had honesty to the bone," he said.
As his campaign gets under way, Mr Huckabee could face challenges within his own party.
Many conservatives will not like the fact that overall, taxes and spending went up during his time as Arkansas governor.
In 2008, Mr Huckabee won eight primaries in socially conservative states but this time he has vowed to focus more on the economy and national security.
To win the Republican crown, he will have to overcome Senators Marco Rubio, Ted Cruz and Rand Paul, as well as former Hewlett-Packard boss Carly Fiorina and retired neurosurgeon Ben Carson.
Jeb Bush has not officially announced but is the frontrunner in the party.
Former Arkansas Governor Mike Huckabee has launched a second attempt at getting the Republican nomination for the presidency.