The Republican president made his case before thousands of supporters at a rally in Florida, calling the state "my second home".
Mr Trump used the announcement to lash out at Democrats, accusing them of trying to "rip your country apart".
Early polls place Mr Trump behind some potential Democratic challengers.
"We are going to keep America great again," the president said at an Orlando rally on Tuesday night. "Tonight I stand before you to officially launch my campaign for a second term as president of the United States."
"Together we stared down a broken political establishment and we restored government by and for the people," he recalled of his first campaign, declaring it "a great political movement".
"As long as you keep this team in place, we have a tremendous way to go. Our future has never looked brighter or sharper."
Mr Trump returned to his 2016 campaign pledge of cracking down on illegal immigration, warning that his Democratic challengers wanted to legalise migrants crossing the southern border.
A day earlier, the president tweeted that authorities would start "removing the millions of illegal aliens who have illicitly found their way into the United States".
What did Trump say about deportations?
Mr Trump tweeted on Monday night that undocumented migrants in the US would be "removed as fast as they come in".
US Immigrations and Customs Enforcement (ICE) typically does not announce raids, and the agency's officials told US media they had been unaware the president would tweet about the plans.
Earlier this month, acting ICE Director Mark Morgan said authorities would target migrants who have received final orders of deportation, including families.
In his Monday night tweets, Mr Trump also contrasted Mexico's "strong immigration laws" - the product of a new agreement to avert US tariffs - with US Democratic border policies.
As a part of the deal, Mexico is deploying 6,000 National Guard personnel to its borders to crack down on Central American migration.
A senior Mexican official told the Associated Press news agency the number of migrants arriving at the US border had already dropped from 4,200 to 2,600 per day.
What's happening in Florida?
Some had camped outside the Amway Center arena in Orlando since early Monday morning.
CBS News reports many of the voters in the queue listed the economy and immigration among their top concerns - issues Mr Trump is sure to address throughout his campaign.
Protesters also attended - and after a successful GoFundMe campaign, the Baby Trump balloon that took to the skies above London during the president's recent UK visit will also put in an appearance.
Florida is a key battleground state and one that Mr Trump won narrowly in 2016.
Tonight in Orlando, Donald Trump officially announced he is seeking another four-year presidential term. This should come as absolutely no surprise, given that he filed re-election paperwork the day after his January 2017 inauguration and has been holding campaign-style rallies pretty much nonstop since moving into the White House.
If Democratic hopefuls can hold multiple official and unofficial kick-off events, however, there's little wonder that Mr Trump - the master of dominating the 24-hour news cycle - wants in on the action.
Traditionally, good numbers on the economy and a nation at peace are a golden ticket to four more years for an American president. That polls, including his own campaign's internal ones, show Mr Trump with an uphill fight on his hands are just a small clue that this is an unusual president running through uncharted political territory.
The presidential race won't begin in earnest for months yet, but this moment in Orlando is as good a time as any to calibrate clocks, check the prevailing conditions and look out on the journey ahead.
What is happening in the polls?
According to Gallup, Mr Trump's approval rating has never been over 46% - and as of last month, it dipped to 40%.
His most favourable polling from Rasmussen puts him at 48% approval.
And when compared to his Democratic challengers, a poll from the president's favourite outlet, Fox News, placed him behind Mr Biden by 10 percentage points and Bernie Sanders by nine.
Elizabeth Warren and Kamala Harris also lead Mr Trump, albeit by a smaller margin.
The president's aides have pointed out he was also written off in opinion surveys back in 2016.
The Trump reportedly campaign fired several of its hired pollsters after leaks showed the president losing to Democrats next year in several key battleground states.
But Mr Trump has maintained his polls "show us leading in all 17 Swing States".