Republican candidate John McCain on Saturday called Lewis' remarks "shocking and beyond the pale."
In a statement issued Saturday, Lewis said McCain and running mate Sarah Palin were "sowing the seeds of hatred and division, and there is no need for this hostility in our political discourse." He noted that Wallace also ran for president.
"George Wallace never threw a bomb. He never fired a gun, but he created the climate and the conditions that encouraged vicious attacks against innocent Americans who were simply trying to exercise their constitutional rights," said Lewis, who is black. "Because of this atmosphere of hate, four little girls were killed on Sunday morning when a church was bombed in Birmingham, Alabama."
One of the seminal events of the civil rights movement was the bombing of Birmingham's 16th Street Baptist Church on Sept. 15, 1963. Four black girls died in the blast, which was linked to a Ku Klux Klan group.
Late Saturday, Lewis released another statement saying it was not his "intention or desire" to directly compare McCain or Palin to Wallace.
"My statement was a reminder to all Americans that toxic language can lead to destructive behavior," he said. "I am glad that Sen. McCain has taken some steps to correct divisive speech at his rallies. I believe we need to return to civil discourse in this election about the pressing economic issues that are affecting our nation."
Lewis' comments follow widely reported examples of anger at McCain rallies that has been aimed at Obama, the first black man to be a major party's nominee for president. During some rallies featuring McCain and Palin, supporters have shouted "traitor," "terrorist," "treason," "liar" and even "off with his head."
The outbursts came amid a harshly personal line of attack against Obama by the Republican campaign. McCain and Palin have said Obama failed to tell the truth about his ties to 1960s radical William Ayers, had a radical agenda on abortion, and wasn't really known to voters. Last weekend, Palin signaled the uptick in the criticism when she charged that Obama was "palling around with terrorists," a reference to Ayers, and that he didn't see the U.S. as others did.
McCain drew boos at a town-hall meeting Friday in Minnesota when he defended Obama after a supporter said he feared what would happen if Obama were elected president. He also cut short a woman who said Obama was an Arab, and he called his rival "a decent, family man."
On Saturday, McCain called on Obama to repudiate Lewis' remarks. While dismissing the comparison to Wallace, Obama campaign spokesman Bill Burton said Lewis was on target in other ways.
"John Lewis was right to condemn some of the hateful rhetoric that John McCain himself personally rebuked just last night, as well as the baseless and profoundly irresponsible charges from his own running mate that the Democratic nominee for president of the United States 'pals around with terrorists,"' Burton said in a statement.
In his remarks, Lewis also said: "As public figures with the power to influence and persuade, Sen. McCain and Gov. Palin are playing with fire, and if they are not careful, that fire will consume us all. They are playing a very dangerous game that disregards the value of the political process and cheapens our entire democracy. We can do better. The American people deserve better."
McCain rejected any comparison to Wallace.
"I am saddened that John Lewis, a man I've always admired, would make such a brazen and baseless attack on my character and the character of the thousands of hardworking Americans who come to our events to cheer for the kind of reform that will put America on the right track," McCain said.
Several times on the campaign trail this year, McCain has praised Lewis, invoking the Congressman's name in connection with Dr. Martin Luther King and telling the civil rights veteran's story during an event in Selma, Ala.
During the primary campaigns, on Martin Luther King Day, CBS News asked all the candidates to . McCain noted that he was in a prison camp in Vietnam when King was assassinated, but referenced Lewis, a disciple of King's.
"I did not know Dr King," McCain said. "But I know John Lewis, and I know what he represents. And John Lewis and I may disagree on some issues, but that's the kind of person I think are true American heroes."
In April, while in Selma, Ala. -- the backdrop for a milestone civil rights march on March 7, 1965 -- McCain , who suffered a fractured skull from a beating during the protest.
In August, while appearing at a forum on faith, McCain was asked to name three "wise people" he would listen to. He cited Lewis as well as Gen. David Petreaus, head of U.S. troops in Iraq, and former eBay CEO Meg Whitman, a top adviser to his campaign.