"He's so far on the fringe," she said in her opening statement. "That's where the contrast comes in."
But in the one-hour forum before the Missouri Press Association, Akin got in his shots as well, accusing McCaskill of often siding with President Barack Obama on such issues as health care reform. Akin said he didn't buy the senator's portrayal of herself as a moderate Democrat.
"Claire can say that she's a '50 percenter,' but when you vote 98 percent of the time with Obama and then tell us that you're a regular 'middle of the roader,' that takes a lot of guts," Akin said.
Joining in the debate was Libertarian candidate Jonathan Dine, who pushed a message of smaller government and lower taxes.
"We do not need politicians telling us who we can love, what to do with our own money or what we can do with our own body," Dine said.
One thing Akin and McCaskill agreed on was that their candidacies offer Missourians a choice between two sharply different directions for the country. Akin described it as the difference between more freedom and "more and more red tape and bureaucracy and agencies and executive orders and taxes and everything.
"It's your choice," he said. "More freedom or more Washington."
McCaskill, however, said voters must decide between a moderate who works with Republicans and is willing to compromise, versus a conservative who works with the likes of U.S. Rep. Michele Bachmann of Minnesota and has said he doesn't like Social Security.
"This election is going to be quite a contrast for Missourians," McCaskill said.
The race attracted national attention last month when Akin, a six-term House member from the St. Louis area, told a TV interviewer that victims of "legitimate" rape have a biological ability to ward off pregnancy.
Akin has apologized repeatedly for the remark and said he misspoke, but was asked early in Friday's forum how much significance voters should place on his comments. Akin said the election is not about a choice of words, but more about voting records that are polar opposites of each other.
McCaskill, he said, needs to take common sense to the nation's Capitol "instead of dragging all of this stuff from Washington, D.C., and dumping it on the state of Missouri and killing jobs and destroying our economy and crushing the American dream."
While acknowledging Akin had apologized, McCaskill said his remarks about rape were telling because they "opened the window to his views" for many voters.
"They say a lot about how he views things, and that's where Missourians need to pay attention," she said.
Rape victims should have access to emergency contraception to avoid pregnancy, but Akin opposes that, she said.
"I believe his view is extreme and out of the mainstream for most Missourians," McCaskill said, pointing out that Akin also wants to abolish the minimum wage, do away with federal student loans and funding for school lunches and privatize Medicare and Medicaid.
Akin countered that tough choices need to be made if America wants to get serious about lowering its $16 trillion debt. He maintained that he favors school lunch programs and college loans, but wants state and local governments to take them over from the federal government.
"I just don't want the federal government to do it," he said. "The mind-set here is the federal government has to do everything for us all the time."
Dine also piled on Akin, remarking that he was "astonished" to learn that the congressman "sits on the Science Committee, yet he fails to understand basic eighth-grade biology."
Akin has come under fire from leaders within his own party, including GOP presidential nominee Mitt Romney, who have called on him to withdraw from the race in the wake of his comments about rape victims. Akin has repeatedly refused to do so and faces an unofficial deadline Tuesday for ending his campaign.
If he withdraws after that day, the state would require him to pay for printing new ballots, which could cost several hundred thousand dollars.
All signs point to Akin continuing his candidacy. On Monday, former House Speaker Newt Gingrich will fly to St. Louis to campaign with Akin.
And Akin got some good news Friday, when South Carolina Sen. Jim DeMint said he might throw his financial support behind Akin. DeMint's Senate Conservatives Fund has raised millions of dollars for candidates.
DeMint also urged the National Republican Senatorial Campaign Committee to reconsider its decision to withdraw its financial backing for Akin.
In the debate, McCaskill and Akin also clashed on Medicare, with Akin again criticizing her support of Obama's health care plan, which includes a proposal to trim $700 billion from Medicare through various cost-saving measures.
Akin portrayed the proposal as a cut to Medicare's bottom line: "Claire wants to take $700 billion out of Medicare, and then wants to crusade as the big hero of Medicare. I don't understand that."
McCaskill, however, called that "the biggest whopper of this campaign season." She said Akin voted for the same idea more than once in approving the House budget bill authored by GOP vice presidential nominee Paul Ryan.
"As President Clinton says, it takes a lot of brass to be against something that you're for," she shot back.
The only other Senate debate scheduled so far will be a televised forum Oct. 18 in the St. Louis area.