The SpaceX Falcon 9 rocket sits at Launch Complex 39A.
The Crew Dragon capsule is bound for the International Space Station, 402 kilometers (250 miles) above Earth.
A launch attempt on Wednesday was called off with less than 17 minutes to go in the countdown because of lightning.
Since then, Nasa astronauts have had to hitch rides aboard Russia's Soyuz spacecraft.
With the SpaceX craft on course to become the first commercial spacecraft to carry humans to the ISS, the U.S. National Aeronautics and Space Administration has said the mission will lay the foundation for "a new era in human spaceflight" where space travel will become less expensive and available to more people.
"Today's launch makes clear the commercial space industry is the future", Trump said, hailing USA billionaire entrepreneur Elon Musk for founding SpaceX in 2002 and making it the first private company to put humans into orbit around the Earth. If successful, Saturday's takeoff will mark the first crewed space mission since the shuttle program was retired in 2011.
NASA astronauts Douglas Hurley and Robert Behnken are ready.
President Trump Announces The End Of Special Relationship With Hong Kong
The Chinese government says the legislation will tackle secession, subversion, terrorism and foreign interference . Protests are simmering again as Hong Kong emerges from its coronavirus shutdown.
"I would be lying to you if I told you I wasn't nervous, " NASA Administrator Jim Bridenstine said.
Trump spoke to SpaceX CEO Elon Musk after the launch.
Nine minutes after liftoff, the rocket's first-stage booster landed, as designed, on a barge a few hundred miles off the Florida coast, to be reused on another flight.
Behnken will be the joint operations commander for the mission, responsible for activities such as rendezvous, docking and undocking, as well as Demo-2 activities while the spacecraft is docked to the ISS. "It's been nine years since we've launched American astronauts on American rockets from American soil, and now it's done. With everything that's going on in this country right now, it's important that we do things extraordinary in life", Wight said.
"On April 14, 2014, the agency signed a property agreement with SpaceX of Hawthorne, California, for use of the launch site for the next 20 years".
United Kingdom astrononaut Tim Peake tweeted: 'You can see the @Space-Station pass over the United Kingdom tonight, 22:10 BST. The Commercial Orbital Transportation Services (COTS) program, started by NASA in 2005, supported the development of commercial cargo vehicles, including the original SpaceX Dragon spacecraft. At 04:55 p.m. EDT (01:55 p.m. PDT), the astronauts will take control of Crew Dragon for the first of two manual flight tests created to show that astronauts can take control in the event of a system's failure. Both companies launched their crew capsules past year with test dummies. "It did not seem likely at the time when we arrived at the astronaut office ... so I think we're living the dream".
"We planted the seeds of today's success during the 2009 Recovery Act, which according to NASA, has saved taxpayers up to $30 billion and invigorated an aerospace industry in Florida that accounts for more than 130,000 jobs in the state", the former vice president said.