His announcement video on Monday featured some of the controversies that have surrounded Mr. Trump during his presidency and on the campaign trail, including the bombshell release of the 2005 "Hollywood Access" tape in which the president made vulgar remarks about women. In the video, a narrator recounts Weld's experience leading MA and shows clips of some of Trump's most controversial comments.
The announcement video also touts Weld's record on helping to fight corruption, particularly Democrat corruption in MA, as well as his connection to President Ronald Reagan, who appointed him to be a "crime-fighting" USA attorney.
But he faces an uphill battle to take over a Republican party that has been refashioned in Mr Trump's image.
Weld said, "I'm announcing that I'm running for president of the United States as a Republican against President Trump in 2020".
"I really think if we have six more years of the same stuff we've had out of the White House the last two years that would be a political tragedy", he said on CNN.
"I would be ashamed of myself if I didn't raise my hand and run", he told Tapper.
Mr Weld's campaign video touts his cross-party credentials as a Republican who was elected in the Democratic stronghold of MA.
The three-minute production contrasts his record with clips of provocative statements by Mr Trump. "A better America starts here".
Party leaders have quickly rejected Weld's campaign which make things look hard for him in the long run.
According to the most recent Gallup poll, 89% of Republican voters approve of the president. His campaign recently reported raising $30 million in the first quarter of this year, while Democrats are raising less money than in previous cycles.
Trump enjoys a almost 90% approval rating among Republicans, according to Gallup.
"The RNC and the Republican Party are firmly behind the president", an RNC spokeswoman said in a statement.
The video also criticized Trump's misogynistic comments about women, his mockery of a reporter with disabilities, and his failed campaign promise to have Mexico pay for a wall on the southern USA border.