Concern about the strength of the U.S. economy, coupled with worries about Ebola and Islamic State militants, are driving the dour mood of a restive electorate. Democrats could pay the price when voters elect 36 senators, all 435 members of the House of Representatives and 36 state governors.
Obama's name is not on the ballot, but his low job approval rating reflects a lack of confidence in his leadership during the sixth year of his presidency. Polls indicate Democrats have less enthusiasm for voting than Republicans, and history shows the party that is in power in the White House in midterm elections usually loses seats.
"There doesn't seem to be a lot of things for people to feel good about," said David Yepsen, director of the Paul Simon Public Policy Institute at Southern Illinois University. "It may not be fair, but they tend to take those kinds of feelings out on the White House, and as a practical matter I think the Senate goes Republican."
In the House of Representatives, Republicans are expected to build on their majority of 233 seats to 199 for Democrats. They also will likely retain their majority in the number of governors' seats they hold in state capitals.
But the heavy campaign action has been in the 100-member Senate, where Republicans need to pick up six seats to reclaim the majority from Democrats and control both chambers of Congress for the first time since the 2006 election. While Republicans are expected to gain seats, as many as eight to 10 Senate races are still considered toss-ups that could go either way.
There is a good chance the party that controls the Senate will not be known on Tuesday night. Senate races with multiple candidates in Louisiana and Georgia, where the winner must get more than 50 percent of the vote, could be forced into runoffs in December or January, respectively.
If Republicans do take control of the Senate, Obama's last two years in office would be complicated by the prospect of even more partisan gridlock, although it could force him to make more compromises with his political opponents.
A Republican-led Senate would be likely to push ahead with approval of the Keystone XL crude oil pipeline, chip away at provisions in Obama's signature healthcare law, and take steps toward a broad rewrite of tax laws.
According to a Reuters-Ipsos poll in late October, just 38 percent of Americans approve of Obama's handling of his job as president, compared to 56 percent who disapprove. Meanwhile, just 24 percent think the country is headed in the right direction, and 61 percent believe it is on the wrong track.
About 58 percent of Republicans are dead certain they will vote, compared to 44 percent of Democrats, the Ipsos poll shows.
Obama's unpopularity has made him politically radioactive on the campaign trail. Democratic candidates have kept him at arm's length in competitive states where Senate control will be determined.
Instead, he has largely been restricted to Democratic fund-raising events, although in recent days he headlined events in friendly states such as Maine, Rhode Island and Michigan. On Sunday, he travels to Connecticut and Pennsylvania.
"I'm not on the ballot this time and this is the last election cycle in which I'm involved as president," said Obama, who was elected to the U.S. Senate in 2004, and to the White House in 2008 and 2012.
"Look, it makes you a little wistful, because I do like campaigning. It’s fun," he said in Portland, Maine, on Thursday night.
Although the White House publicly predicts Democrats will hold on to the Senate majority, people who have visited the West Wing recently say a grim mood has settled in.
But Democrats said the number of close races still gives them a shot to hold the Senate, particularly if their vaunted, data-driven voter turnout operation tips some key races in their favor.
"The Republicans have done a good job of making the president and his agenda the issue. The only way Democrats are gong to win in the end is if they remind voters that all politics are local," said Democratic strategist Jim Manley.
The Republican drive to a Senate majority is focused on defeating Democratic incumbents in what polls show are tight races in Louisiana, Arkansas, Alaska, North Carolina, New Hampshire and Colorado, and winning a fierce battle for the open Iowa seat of retiring Democrat Tom Harkin.
Democrats are trying to make the task harder for Republicans by beating Senate Republican leader Mitch McConnell in Kentucky - he has a small but consistent lead in recent polls - and winning the Georgia Senate seat being vacated by retiring Republican Saxby Chambliss.
Republicans who began the year campaigning against the rocky rollout of Obama's healthcare law have ended it by emphasizing what they call Obama's failed leadership.
"The president wanted to frame this election around this battle about which party was better positioned to represent middle-class voters," said Republican strategist Kevin Madden. "What's happened instead is we've seen the country lurch from crisis to crisis and as a result the public’s confidence in the president and Washington as an institution has eroded."