The Republican president made his case before thousands of supporters at a rally in Florida, calling the state “my second home.”
Trump used the announcement to lash out at Democrats, accusing them of trying to “rip your country apart.”
Early polls place Trump behind some potential Democratic Party challengers.
He entered the stage with his wife Melania, who said she was “excited” to be first lady for six more years.
Senior figures from the White House, including Vice President Mike Pence and outgoing press secretary Sarah Sanders, also spoke at the rally.
“Tonight I stand before you to officially launch my campaign for a second term as president of the United States,” Trump told supporters in Orlando. “I promise you I will never ever let you down.
“We are going to keep America great again.”
During his roughly 80-minute speech, Donald Trump reiterated key themes of his winning 2016 campaign.