Until the rape comment, Akin was considered the favorite to beat McCaskill in a state that has trended Republican and voted for Republican presidential candidate Mitt Romney on Tuesday.
But the race reversed course after Akin's comment to a television station that women have natural defenses against pregnancy from "legitimate rape." The comment drew scorn from state and national Republican leaders who called on him to drop out of the race.
Akin apologized for his remarks but refused to withdraw. He regained support of some top Republicans but lost significant financial backing.
McCaskill had drawn heat for failing to pay taxes on a private family plane, which did not sit well with state residents, Petrocik said.
People interviewed at St. Louis-area polling stations on Tuesday said Akin's rape comments were important to their vote.
"Seeing Akin's attitude toward woman in general, voting for him would be impossible," said Mary Mitchell Bartley, a St. Louis historic neighborhood preservationist who had backed previous Republican candidates.
Akin's loss was another blow to Republicans, who had hoped to make a net gain of four U.S. Senate seats to take the majority in the upper chamber.