Speaking from space to Crew Dragon chief engineer Bala Ramamurthy, Mr Hurley said the launch was incredible.
He said: “Appreciate all the hard work and thanks for the great ride to space.”
According to NASA, some 10 million people tuned in to watch the launch online.
US President Donald Trump was also present at the Kennedy Space Center to watch the landmark event in person.
NASA administrator Jim Bridenstine said: “I think he’s the only sitting President to watch American astronauts launch on a brand new rocket that has never launched before. That’s a big risk, you know.”
Astronauts Behnken and Hurley will spend about 19 hours in orbit before they reach the space station.