All 435 House of Representatives seats, 33 of 100 Senate seats and 36 state governorships are at stake.
Democrats must pick up 15 House seats and six Senate seats to reclaim control of Congress from Republicans.
Several polls show Democrats with a big edge over Republicans, with voters disillusioned over the Iraq war and displeased with President George W. Bush's leadership.
If Democrats take the House, they vow to confront Mr Bush during his final two years in office on such matters as the rising cost of health care and a college education as well as the increasingly unpopular Iraq war.
Democrats have dubbed their campaign agenda "A new direction for America." It includes raising the federal minimum wage for the first time in a decade, ending tax giveaways to big oil companies and implementing stalled proposals by the 9/11 commission to secure ports and borders.
Mr Bush maintains that his administration and the Republican-led Congress have boosted the economy and kept the United States safe, and those issues are of greatest importance to voters. He has depicted Democrats as soft on terrorism and accused them of pushing a "cut-and-run" approach to Iraq by calling for a US troop withdrawal timetable he has refused to set.
Mr Bush has promised to keep taxes low and make recent tax cuts permanent, while charging the Democrats will raise taxes if they win control of Congress.
Polls are now open and will begin to close at at 6 p.m