Speaking to Democrats at their annual Truman Days dinner in Kansas City, McCaskill dubbed the trio the "most extreme" Republicans Missouri has ever seen.
"They make John Ashcroft look like a liberal," she said.
McCaskill said the her opponents - Sarah Steelman, Todd Akin, and John Brunner - are proving her point when they fight over who is the true "Tea Party candidate."
McCaskill said the 2012 election will be a deciding factor in Missouri's political influence as a swing state moving forward.
"We're going to hold onto Harry Truman's senate seat," she said.
McCaskill's campaign has already invested in television time and McCaskill is expected to officially hit the campaign trail early next month. Her campaign has leased a campaign bus, formerly used by Roy Blunt in his successful Senate bid in 2010, for the summer.
The annual dinner, a fundraiser for Jackson County Democrats, attracted a crowd of about 500. Former Virginia Governor and U.S. Senate candidate Tim Kaine, a Kansas City native, gave the keynote speech, urging Democrats to support their U.S. Senate candidates in this year when much of the attention is focused on the presidential race.