Vice President Kamala Harris swore Nelson in as the new NASA administrator Monday morning.
"To have the president and vice president have this kind of confidence in an old buddy from the Senate is indeed one of the high honors that anyone could have," Nelson said after being sworn in.
Last week, the Senate confirmed Nelson, agreeing to President Joe Biden's choice to lead the space agency by consensus without a roll call vote.
"I am honored by the President's nomination and the Senate vote," Nelson said in a statement shortly after his confirmation. "I will try to merit that trust. Onward and upward!"
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Nelson is NASA's 14th administrator, succeeding another former member of Congress, Jim Bridenstine, a Republican from Oklahoma. Nelson currently serves on the NASA Advisory Council.
Nelson promised, when nominated, to "help lead NASA into an exciting future of possibilities." The space agency is working to send astronauts back to the moon this decade.
"Its workforce radiates optimism, ingenuity and a can-do spirit," Nelson said. "The NASA team continues to achieve the seemingly impossible as we venture into the cosmos."
Nelson, 78, grew up near Cape Canaveral and was serving as a Democratic congressman when he launched aboard space shuttle Columbia on Jan. 12, 1986. His commander was Charles Bolden Jr., who later served as NASA administrator under President Barack Obama - at Nelson's urging.
Just 10 days after their flight ended, the space shuttle Challenger failed shortly after liftoff and all seven astronauts were killed.
Nelson, who has a law degree and is a former captain in the U.S. Army Reserve, served six terms in the House of Representatives from 1979 to 1991. He was elected in 2000 to the Senate, where he served until his defeat in 2018 by former Florida Gov. Rick Scott.
The Associated Press contributed to this report.