Shares on Wall Street plummeted, with the Dow registering its steepest points fall - 777.68 - in history and the S&P 500 having its worst day in 21 years.
Republican and Democratic opponents of the government's proposition to offer struggling US financial firms a $700bn bail-out combined to doom the bill by 228 votes to 205, despite George Bush, the US president, pressing for its passage.
McCain took aim at Obama, who he accused of sabotaging the bill by introducing partisan politics into the discussions.
"Senator Obama and his allies in congress infused unnecessary partisanship into the process," he said after the House of Representatives rejected the bill.
"Our leaders are expected to leave partisanship at the door and come to the table to solve our problems.
"Now is not the time to fix the blame, it's time to fix the problem."
A number of US financial firms have faced collapse after receiving losses stemming from the sub-prime mortgage crisis, when people took out high-interest loans they were unable to repay.
The losses have spread to international financial firms, causing chaos in global markets.