Speaking in Virginia on Sunday, he said it would be "very hard for Senator Clinton to break out of the politics of the past 15 years".
"Senator Clinton starts off with 47 per cent of the country against her," he said.
"That's a hard place to start."
The next contests take place on Tuesday in Virginia, Maryland and the District of Columbia, states with high numbers of independent and African American voters expected to favour Obama.
The Clinton camp, meanwhile, is eyeing March 4 votes in Ohio and Texas, both of whom command a higher number of delegates.
In announcing the campaign shake-up on Sunday, Clinton said Maggie Williams will take over from Patti Solis Doyle to manager her bid for the White House.
Solis Doyle would stay on as a senior advisor for the rest of the contest, added the former US first lady.
|Clinton replaced her campaign manager|
to blunt Obama's momentum [AFP]
"Patti Solis Doyle has done an extraordinary job in getting us to this point, within reach of the nomination, and I am enormously grateful for her friendship and her outstanding work," she said.
Williams, who served as Clinton's White House chief of staff, will start running the campaign this week.
Clinton said in the statement "I am lucky to have Maggie on board and I know she will lead our campaign with great skill towards the nomination."
Aides denied there was trouble in Clinton's campaign operations, saying that Solis Doyle had volunteered to leave, and not pressured to do so.
Clinton had a big showing on Super Tuesday on February 5 when she won New York, California and New Jersey, but Obama prevailed by winning the popular votes in more contests.
In the Republican race, Mike Huckabee, a former Arkansas governor, won contests in Louisiana and Kansas on Saturday.
He thus dealt setbacks to John McCain, the frontrunner.
"This race is far from being over," Huckabee said after crushing McCain in Kansas.
McCain, an Arizona senator, became the all-but-certain nominee late last week after his chief rival, Mitt Romney, a former Massachusetts governor, withdrew from the race.