The gunman, who had posted angry messages against President Donald Trump and other Republicans on social media, opened fire on a group of Republican lawmakers and colleagues at a baseball field in Alexandria, Virginia, outside Washington. He was wounded in a gunfight with Capitol Hill police at the scene and later died.
Scalise was shot in the left hip, suffering broken bones, injuries to internal organs and severe bleeding.
He underwent surgery but would need further operations, the MedStar Washington Hospital Center said.
"Rep. Steve Scalise, one of the truly great people, is in very tough shape - but he is a real fighter. Pray for Steve!" Trump said on Twitter after visiting the hospital on Wednesday night.
The gunman, identified by police as 66-year-old James Hodgkinson from the St. Louis suburb of Belleville, Illinois, fired repeatedly at the men playing on the baseball field on Wednesday morning.
Congressmen at the ballpark described hearing loud noises like the sound of firecrackers and 15 to 20 people lying on the ground and realizing they had only baseball bats to defend themselves against bullets.
"When he started shooting, he was shooting to kill people. And thank God he wasn't a very good shot," said Representative Joe Barton, the Republican team's manager.
Also wounded were a congressional aide and one former aide who now works as a lobbyist, officials said. One Capitol Hill police officer suffered a gunshot wound and another officer twisted an ankle and was released from a hospital, police said.
"It was not only chaotic but it was a combat situation," Alexandria Police Chief Mike Brown told reporters.
'IT'S GOT TO STOP'
While police and the Federal Bureau of Investigation said it was too early to determine whether it was a deliberate political attack, the shooting intensified concerns about the sharp divide and bitter rhetoric in U.S. politics.
FBI special agent Tim Slater declined to comment on whether the gunman had a vendetta against Republicans.
"We continue to actively investigate the shooter's motives, acquaintances and whereabouts that led to today's incidents," Slater told reporters. No one else was in custody, he said.
The gunman was believed to have been in the Alexandria area since March, Slater said. Investigators believe that the suspect had been living out of his vehicle.
Wednesday's shooting revived debate about gun rights in America. Virginia's Democratic governor, Terry McAuliffe, urged gun control measures.
Scalise has been a strong opponent of gun control measures.
Hodgkinson had raged against Trump on social media and was a member of anti-Republican groups on Facebook including, "The Road to Hell Is Paved With Republicans," "Terminate The Republican Party," and "Donald Trump is not my President," a search of his Facebook profile showed.
As businessman Trump rose to become the Republican nominee in the 2016 presidential election, his brash style and outspoken views on immigration and other policies led to mass protests, including on the weekend of his inauguration in January.
The charity ballgame between a Republican team and a Democratic team will go ahead as scheduled on Thursday at Nationals Park, home of the Washington Nationals Major League Baseball team.
Representative Tim Ryan, who early on Wednesday was practicing for the ballgame with fellow Democrats, told reporters that Washington politicians needed to cool their rhetoric.
"We've got to get back to ... where things aren't so personal and we're so judgmental of each other. It's got to stop. A member of the U.S. Congress got shot because they didn't like (his) political views," Ryan said.
CALLS FOR UNITY
Trump, who announced the gunman's death, called for unity. "We are strongest when we are unified and when we work together for the common good," he said.
In a show of bipartisanship, Republican House Speaker Paul Ryan said on the floor of the House: "An attack on one of us is an attack on all of us." The House's top Democrat, Nancy Pelosi, echoed Ryan's message.
The shooting happened shortly after 7 a.m. There were 20 House members and two senators present, and the shooting lasted about 10 minutes, said Barton.
Two lawmakers who were at the scene, Representatives Ron DeSantis and Jeff Duncan, indicated there might have been a political motive in the attack.
Duncan said that as he left the field, the man who would later open fire approached him in the parking lot. "He asked me who was practicing this morning, Republicans or Democrats, and I said: 'That's the Republicans practicing,'" Duncan told reporters. DeSantis gave a similar account.
Senator Bernie Sanders, an independent who sought the 2016 Democratic presidential nomination, said he had been told that Hodgkinson had served as a volunteer with his campaign.
"Let me be as clear as I can be: Violence of any kind is unacceptable in our society and I condemn this action in the strongest possible terms," Sanders said.
Ryan, the House speaker, is reviewing rules on how rank-and-file lawmakers can increase their personal security, according to several lawmakers.
"Members get threats on a regular basis and have trouble determining which are real," House Democratic whip Steny Hoyer told reporters.
'HEROISM' OF POLICE
The shooting took place at Eugene Simpson Stadium Park in the Del Ray neighborhood of Alexandria, across the Potomac River from Washington.
Representative Mo Brooks told CNN that during batting practice, he heard a "bam" and then a quick succession of shots and saw the gunman shooting through the holes in a chain link fence.
When Scalise was shot, he went down on the infield between first and second base, then dragged himself into the grassy outfield as the incident unfolded, leaving a trail of blood, Brooks said.
Two Capitol police officers who were there to provide security for the lawmakers engaged the gunman with pistols, Brooks said.
"But for the Capitol police and the heroism they showed, it could very well have been a large-scale massacre. All we would have had would have been baseball bats versus a rifle. Those aren't good odds," Brooks said.
Wednesday's attack was the first shooting of a member of Congress since January 2011, when Democratic Representative Gabby Giffords was seriously wounded in an assassination attempt at a gathering of constituents in Tucson, Arizona. Six people were killed. Giffords resigned from Congress and became an activist for gun restrictions.