Kelly flew combat missions during the Gulf War as a naval aviator before being selected as a NASA Space Shuttle pilot in 1996.

In January 2011, Kelly's wife, then-Arizona Representative Gabby Giffords, was shot and nearly killed in an assassination attempt in Arizona.

[10][11] On June 21, 2011, Kelly announced his retirement from both the Navy and NASA, effective October 1, citing Gabby Giffords's needs during her recovery from the attempt on her life that January.

The Expedition 3 crew officially ended their 117-day residency on board the ISS on December 8 as their custom Soyuz seat-liners were transferred to Endeavour for the return trip home.

The transfer of the Expedition 4 seat-liners to the Soyuz return vehicle attached to the station marked the official exchange of crews.

Mission managers extended Endeavour's flight duration to 12 days to allow the crew to assist with additional maintenance tasks on the station, including work on a treadmill and replacing a failed compressor in one of the air conditioners in the Zvezda Service Module.

[17]The mission's main purposes were to test new safety and repair techniques introduced after the Columbia disaster and to deliver supplies, equipment, and European Space Agency astronaut Thomas Reiter from Germany to the ISS.

[18] During the STS-121 mission to the ISS, the crew of Discovery continued to test new equipment and procedures for the inspection and repair of the thermal protection system that is designed to increase the shuttles' safety.

After liftoff, inspectors discovered that bricks and mortar from the launch pad's base had been thrown as far as the perimeter fence, a distance of 1,500 feet (457 m).

President Barack Obama visited the Kennedy Space Center on April 29 on a trip with the original intention of watching the Endeavour launch.

[2] He announced his retirement on his Facebook page, writing: "Words cannot convey my deep gratitude for the opportunities I have been given to serve our great nation.

[44] In 2015, Kelly and Martha Freeman co-wrote Astrotwins: Project Blastoff, a fictional story about twins Scott and Mark who build a space capsule in their grandfather's backyard and try to send the first kid into orbit.

[46] Kelly was a co-founder and strategic advisor of Tucson-based high-altitude balloon near-space exploration company World View Enterprises.

[50] From 2011 to 2016, Kelly delivered paid speeches in the U.S. and in China on behalf of Shaklee, a multi-level marketing distributor of nutritional supplements.

[51][52] Separately, Kelly has also delivered paid speeches to bank Goldman Sachs, the Mortgage Bankers Association, and drug company AmerisourceBergen.

[53] In January 2013, weeks after the Sandy Hook Elementary School shooting, Kelly and Giffords started a nonprofit political action committee, Americans for Responsible Solutions (ARS).

Kelly is the fifth retired astronaut to be elected to Congress, after John Glenn, Harrison Schmitt, Bill Nelson, and Jack Swigert.

[68] On December 9, Kelly voted "no" on a resolution blocking President Donald Trump from selling $23 billion in drones to the United Arab Emirates.

[70] In January 2023, three bills regarding Indian tribes, introduced by Kelly and fellow Arizona Senator Kyrsten Sinema, were signed into law by President Joe Biden.

[71] During the 117th Congress, Kelly co-sponsored several legislative bills that were supported by both parties and became law; these bills included those on the topics of mandating de-escalation training for law enforcement, updating ocean shipping governance, combating human trafficking, and reimbursing people suffering from radiation from atomic weapon tests; during the 118th Congress, Kelly co-sponsored the bipartisan END FENTANYL Act, passed in 2023.

[85][86][87] Since joining the Senate, he supported abolishing the filibuster in order to pass voting rights legislation[88] and a federal minimum wage increase to $15 per hour.

[96] In a 2021 Greenpeace exposé,[97] Kelly was one of 11 U.S. senators ExxonMobil Senior Director for Federal Relations Keith McCoy called "crucial" to the company.

[100][101] Kelly became an outspoken advocate for gun control after the attempted assassination of his wife, former U.S. Representative Gabby Giffords, in the 2011 Tucson mass shooting.

[102] Kelly voted for the Bipartisan Safer Communities Act in response to the Robb Elementary School shooting in Uvalde, Texas.

[111] Kelly married U.S. Representative Gabby Giffords of Tucson on November 10, 2007, in a ceremony presided over by Rabbi Stephanie Aaron and attended by his STS-124 shuttle crew and former Secretary of Labor Robert Reich.

[116][117] On February 4, Kelly described the previous month as the hardest time of his life[118] and expressed his gratitude for the enormous outpouring of support, good wishes and prayers for his wife.

"[120] From the time he arrived in Tucson, Kelly sat vigil at his wife's bedside as she struggled to survive and began to recover.

Kelly sat between First Lady Michelle Obama and Secretary of Homeland Security Janet Napolitano, the former governor of Arizona.

He said that before the attack, "I thought the world just spins and the clock just ticks and things happen for no particular reason", but that, in Tucson, as he found himself wandering in makeshift memorials and shrines filled with Bibles and angels, "You pray where you are.

[120] In response to a question on February 4, 2011, about civility in politics, Kelly said, "I haven't spent a lot of time following that, but I think that with something that was so horrible and so negative, and the fact that six people lost their lives including a nine-year-old girl, a federal judge, Gabby's staff member Gabe—who was like a younger brother to her—it's really, really a sad situation.