[29] Nelson was elected to the U.S. House of Representatives in 1978 in the open 9th congressional district after the five-term Republican incumbent, Louis Frey Jr., chose to run for governor of Florida rather than for reelection.

In 1988, Bill Nelson criticized President Reagan's policy to export American satellites for launch on China's Long March rockets.

[37] Florida's resign-to-run law compelled Nelson to submit his resignation as Treasurer, Insurance Commissioner and Fire Marshal early in 2000 when he began to campaign for the U.S. Senate seat.

[38] Evangelical Christian activist James Dobson declared that Democrats, including Nelson, would be "in the 'bull's-eye'" if they supported efforts to block Bush's judicial nominees.

[39] Nelson's refusal to support efforts in Congress to intervene in the Terri Schiavo case was seen as "a great political issue" for a Republican opponent to use in mobilizing Christian conservatives against him.

In March 2011, Biden was reported as having said that if Nelson lost in 2012, "it means President Obama and the Democratic presidential ticket won't win the key battleground state, either.

He ran unopposed in the Democratic Party primary on August 28[50][51] and faced Florida Governor Rick Scott (a Republican) in the general election on November 6.

NASA Administrator Jim Bridenstine praised his appointment, saying, "Nelson is a true champion for human spaceflight and will add tremendous value as we go to the Moon and on to Mars.

[10] Nelson and Susan Collins introduced legislation in 2015 that would "make it easier for smaller businesses to cut administrative costs by forming multiple-employer 401(k)-style plans.

The proposal would also cap average annual premium increases at 15 to 18 percent and allow insurance-rates subsidies based on current flood maps.

"[88] In September 2014, Nelson said the U.S. should hit back at the Islamic State (ISIS) immediately, because "the U.S. is the only one that can put together a coalition to stop this group that's intent on barbaric cruelty.

[90] Standing outside the Orlando Pulse nightclub immediately after the June 2016 massacre there, Nelson called Omar Mateen a "lone wolf", and when asked if it was an act of jihad, said he could not confirm that.

[104] He argued against the $6 billion development of the Commercial Crew Program proposed by the Obama administration and for a NASA-developed heavy lift rocket built on Constellation's inheritance, which was later included in the NASA Authorization Act of 2010 and became SLS.

[105] 11 years later, Charles Bolden (NASA administrator in 2010) said that Nelson's skepticism was common in Congress at the time and refused to call him an opponent of commercial crew.

[107] In September 2011, Nelson and Senator Kay Bailey Hutchison led the push to continue the development of Constellation's Ares V SLV in the form of Space Launch System.

[119] In March 2017, Nelson co-sponsored the Israel Anti-Boycott Act, Senate Bill 720, which permits U.S. states to enact laws that would require contractors to sign a pledge saying that they will not boycott Israeli goods or their contracts will be terminated.

[129][130] In response to the 2016 Pulse nightclub shooting in Orlando, Nelson expressed remorse that the Feinstein Amendment, which would have banned the sale of guns to people on the terrorist watch list, and a Republican proposal to update background checks and to create an alert for law enforcement when a person is placed on the terrorist watch list, had failed to pass the Senate.

[132] In October 2017, after the Las Vegas shooting, Nelson and Dianne Feinstein sponsored a bill to ban bump stocks for assault weapons.

"[133] Nelson spread misinformation via Twitter after the Parkland high school shooting in 2018, falsely claiming that shooter Nikolas Cruz wore a gas mask and tossed smoke grenades as he shot people.

Along with 16 Florida congress members from both parties, he urged the Trump administration to keep the eastern Gulf of Mexico off limits to oil and gas drilling.

"Drilling in this area," they wrote, "threatens Florida's multibillion-dollar tourism-driven economy and is incompatible with the military training and weapons testing that occurs there.

"[11][137][138] In 2011, Nelson co-sponsored the RESTORE Act, which directed money from BP fines to states affected by the Deepwater Horizon oil spill.

"[142][143] After Hurricane Maria in 2017, Nelson and Rubio agreed that Trump had taken too long to send the U.S. military to Puerto Rico to take part in relief efforts.

[150] In January 2018, Nelson voted to reauthorize the Foreign Intelligence Surveillance Act, which allows the National Security Agency to extend a program of warrantless spying on internet and phone networks.

[153] The incident fueled debate amid a burgeoning space race narrative,[154] with China’s comprehensive lunar initiatives, including the Chang'e missions, and the Artemis program, both vying to send astronauts back to the moon.

[156] In March 2018, Nelson voted against Bernie Sanders's and Chris Murphy's bill to end U.S. support for the Saudi-led intervention in the Yemeni civil war.

[163] A government official familiar with the intelligence told The McClatchy Company that Russian hackers had penetrated some of Florida's county voting systems in 2016.

"[159] The Tampa Bay Times reported that leaders of the Senate Intelligence Committee had told Nelson of a penetration of some of Florida's voter registration databases in 2016.

[159] Department of Homeland Security Secretary Kirstjen Nielsen and FBI director Christopher Wray denied Nelson's claims in a letter to Florida election officials.

[158] The Foundation for Accountability and Civic Trust, a conservative watchdog group, filed an ethics complaint against Nelson, saying that he "discussed classified information or made it up".