In a speech Saturday night to a GOP crowd in his hometown, the Kentucky Republican derided Obama for performing "Clintonian back flips" to portray himself as a moderate, but said it's yet to be seen whether the new tone is "rhetoric or reality."
McConnell, who in the past has touted his ability to bring federal spending to Kentucky, took a hard line on cutting federal spending. He said the Democratic president's credentials on spending and debt "are horrible, and he earned it."
But McConnell said that congressional Republicans - who took control of the House and increased their numbers in the Senate following last year's election - are "prepared to do business" with Obama.
"And to the extent that the president wants to do what we think is right for America, we won't say 'no' simply because there's an election coming along," said McConnell.
After the fall elections, McConnell was criticized for saying his No. 1 goal was to make Obama a one-term president. But he later worked with the president to push through an extension of Bush administration tax cuts, including for top-earners.
Still, McConnell drew cheers from the partisan crowd when he declared: "The legislative agenda of Barack Obama is over."
McConnell also laid out the strategy of Senate Republicans, saying, "Whatever the House can get out of the House with a majority vote is the goal of the Senate."
While Republicans remain in the minority in the Senate, McConnell said Democratic senators facing re-election next year have a political motivation to join GOP lawmakers in pushing for spending cuts.
"We'll see how many of them come over and join us and begin to tackle our annual deficit," he said.
McConnell said the national debt has grown rapidly with the stimulus spending under Obama, and yet national unemployment remains stubbornly high.
McConnell warned that cutting federal spending won't come without some pain.
"Everybody is going to have to do with less if we're going to get this job done," he said. "And we need to get it done."