The 12-nation trade deal was a linchpin of former President Barack Obama's Asia policy.
"Great thing for the American worker what we just did," said Mr Trump as he dumped the pact with a stroke of a pen.
He also cut funding for international groups that provide abortions, and froze hiring of some federal workers.
Mr Trump's executive order on TPP was largely symbolic since the deal has not been ratified by a divided US Congress.
During his presidential campaign, he criticised the accord as a "potential disaster for our country", arguing it harmed US manufacturing.
His action won some plaudits from the left as well as the right.
Democratic Senator Bernie Sanders told the BBC he backed it because trade deals like this have been a "disaster" and cost millions of jobs.