Columbia shot off its oceanside launch pad and into a clear blue sky at 10:39 a.m. On board were seven astronauts, including Ilan Ramon, a colonel in Israel's air force and a former fighter pilot.
Mission control astronaut Charlie Hobaugh welcomed Ramon a tight fraternity.
"A big welcome to Ilan as you join the international community of human spaceflight," he radioed.
Shuttle commander Rick Husband replied with a subtle reminder that Ilan Ramon is one of just four rookies aboard this flight.
"We made sure we welcomed everybody to space and they're all doing great," he said.
Security has been tight at Cape Canaveral since the Sept. 11 attacks, but it was even tighter for this launch because of the always turbulent Middle East situation, reports CBS News Correspondent Peter King. There were extra guards with machine guns, a heavier-than-usual escort on the way to the launch pad, and officers from the Air Force, Coast Guard, and hundreds of local law enforcement agencies.
Air Force officials said there were no security breaches.
Ramon's wife and their four children were among the approximately 300 Israelis who traveled to Cape Canaveral to cheer him on.
"It gave me goose bumps," Jerusalem resident Devorah Meyer told CBS News Correspondent Robert Berger after the lift-off.
"I am both proud and amazed," said Kent Allen. "It's also a bright light in a gloomy general situation in Israel, so I'm personally thrilled."
"Just the idea of astronaut going into space, we can focus, just get our eyes off this country and all of its problems," said Pamela Suran.
"This is a great day for Israel," added Yaffa Reuven.
Israeli ambassador Danny Ayalon — tailed by seven sheriff's department cars — met with reporters following liftoff and marveled at the sight of the white exhaust plume against the blue sky. "These are our national colors," he said. "It was very, very moving."
Earlier in the morning, Ramon and his six U.S. crewmates rode to the pad under heavy police escort. A space center worker waved an Israeli flag as the "astrovan" passed in front of the launch control center.
Despite the presence of a large SWAT team, the entire shuttle crew looked relaxed. Ramon waved and gave a thumbs-up.
Ramon, 48, the son of a Holocaust survivor, was among the Israeli pilots who bombed the Iraqi nuclear reactor in 1981, according to a senior Israeli government official speaking Thursday on condition of anonymity. The Israel Space Agency wanted a military pilot for its first astronaut and, with the Israeli air force's help, picked him for the job in 1997.
CBS News Space Consultant Bill Harwood reports Ramon will try to keep kosher and observe the Sabbath during the flight.
"All that food has to approved by NASA and prepared specially for use on the shuttle, but he said he is going to try to observe [the kosher laws] and have some joint meals together in the sense of the Sabbath," said Harwood.
However, there's a sunrise and sunset about every 90 minutes when the shuttle is in orbit.
"All those sunsets and sunrises up in space every single day, it doesn't work as it does on the earth, but he's going to make a symbolic effort to honor some of those traditions," Harwood said.
Columbia's flight initially was targeted for mid-2001 but was repeatedly delayed, most recently by the grounding of the entire space shuttle fleet last summer.
"If there was ever a time to use the phrase 'all good things come to people who wait,' this is the one time," launch director Mike Leinbach told the astronauts just before liftoff. "Good luck and Godspeed."
Replied shuttle commander Rick Husband: "The Lord has blessed us with a beautiful day here, and we're going to have a great mission."
It is the first time in three years that NASA is launching a shuttle that is not going to the international space station or working on the Hubble Space Telescope.
Sixteen days is a long duration flight by shuttle standards, says Harwood.
"The crew is going to work in two shifts, so it's a 24/7 operation. They'll get a bit of data out of that," he said. "It's not as good as being up there for six months on the station, but they'll still get a lot of useful data on the long-term effects of weightlessness."
One of the primary experiments is sponsored by the Israel Space Agency. Onboard cameras will measure desert dust in the atmosphere to gauge the effect on climate change.
"There are quite a few critters on board, many of them from student-sponsored experiments," said Harwood. "There are silkworms on board, carpenter bees from Europe, there's an ant colony on this flight, believe it or not, from my high school in New York, pretty much just studying the effects of weightlessness on animal behavior and development. It's pretty interesting stuff."
Altogether, more than 80 experiments from around the world are planned.
Columbia is due back at Kennedy Space Center on Feb. 1.
CBS News Space Consultant William Harwood has covered America's space program full time for more than 15 years, focusing on space shuttle operations, planetary exploration and astronomy. Based at the Kennedy Space Center in Florida, Harwood provides up-to-the-minute space reports for CBS News and regularly contributes to Spaceflight Now and The Washington Post.