Kelly and pilot Greg Johnson, spacewalkers Mike Fincke, Drew Feustel and Greg Chamitoff, and Italian astronaut Roberto Vittori are headed for the International Space Station, where they are set to conduct four spacewalks and test a new rendezvous system for Orion, the capsule NASA planned as its next-generation spacecraft.
Endeavour, its external fuel tank and solid rocket boosters will weigh more than 4.5 million pounds at liftoff, but reach 100 miles per hour in 10 seconds, NASA says.
The shuttle will head northeast, gaining speed and altitude as it skirts the Eastern Seaboard, passes over Halifax, Nova Scotia, and heads out over the Atlantic Ocean. On the way, it will jettison its rocket boosters and external fuel tank, which will plunge into the sea.
In orbit, Endeavour will reach speeds of over 17,200 miles per hour, or 25 times faster than the speed of sound.
NASA says the mission is the most scientifically significant since the flight to repair the Hubble Space Telescope two years ago.
The shuttle is carrying a $2 billion alpha magnetic spectrometer, an instrument that will be installed on the space station. It could prove or disprove the Big Bang Theory of how the universe was formed.
"We think we are going to find something really exciting, but we just don't know what it is," said Nobel prize-winning physicist Samuel Ting, whose research led to the design of the device.
Endeavour's flight will be the 134th for a U.S. space shuttle. Shuttle Discovery ended its career earlier this year; Atlantis is expected to make its trip to space in June.
NASA recently announced the retirement homes for its shuttle fleet. Endeavour will head to the California Science Center near Los Angeles after it's decommissioned. Discovery will go to the Smithsonian National Air and Space Museum outside Washington, D.C., and Atlantis will remain on display at the Kennedy Space Center in Florida.