The Illinois senator cut deeply into rival Clinton's political bedrock, splitting the support of white women almost evenly with the former first lady and running well among working class voters in the Midwestern state, according to polling place interviews.
John McCain, the Republican frontrunner, also won in Wisconsin and Washington state, moving him one step closer to getting the presidential nomination from his party.
"Thank you Wisconsin for bringing us to the point where even a superstitious naval aviator can claim with confidence and humility that I will be our party's nominee for president," McCain, a former Navy fighter pilot and Vietnam prisoner of war, told supporters in Columbus, Ohio.
The Arizona senator now holds an essentially insurmountable lead in delegates over Republican rivals Mike Hucakbee and Ron Paul.
In his victory remarks on Tuesday, McCain took direct aim at Obama.
"I will fight every moment of every day in this campaign to make sure that Americans are not deceived by an eloquent but empty call for change," the Republican nominee-in-waiting said in a thinly veiled attack on Obama.
His words seemed to echo Clinton's, who all but conceded Wisconsin even before the release of results.
Addressing supporters, Clinton never mentioned her Wisconsin loss and instead attacked Obama's oratory as empty and meaningless.
The primary campaign "is about picking a president who relies not just on words but on work - on hard work to get America back to work", she told a Youngstown, Ohio, rally on Tuesday night, adding that the "best words in the world are not enough" unless they are matched with action.