Polling booths open on Tuesday, November 4, beginning 06:00 Eastern time.
The Republicans, who already control the House of Representatives, need to gain just six seats to take the Senate.
Meanwhile the Democrats are battling to stay ahead as President Barack Obama’s approval ratings fall to the lowest they have been since he was elected.
Many analysts predict a Republican victory as Barack Obama’s popularity rate fails to climb much above 40%, despite recent improvements in the economy.
“This is a referendum on the president,” Republican senator and potential 2016 presidential candidate Rand Paul told NBC’s Meet the Press at the weekend.
Democrats say their proven ability to rally their supporters ahead of elections could still give them the advantage.
“Grab everybody you know, get them out to vote, don’t stay home, don’t let somebody else choose your future for you,” Barack Obama said during a campaign rally on November 2.
Without the focus of a presidential campaign, the midterms – which are named because they fall in the middle of a presidential term – typically see a low voter turnout.
They also typically favor the party that is not in power.
This year, a little over a third of the 100-seat Senate, all 435 members of the House of Representatives, 36 out of 50 state governors, and countless state and local offices are up for election.
The most closely watched action will be the races that will determine control of the upper chamber of Congress, the Senate.
The Democrats currently hold a five-seat majority in the Senate, meaning the Republicans need only six seats to take control.
As the Republicans already have a convincing hold over the lower House of Representatives, a win in the Senate would give them the power to shut down Barack Obama’s policies in the last two years of his term.
Aside from Barack Obama’s unpopularity, there is no single issue that dominates this midterm poll.
Instead voters will be swayed by a broad variety of concerns including the economy, the environment, immigration, foreign policy, abortion and healthcare.
The most competitive Senate races are expected to take place in the states of North Carolina, Arkansas, Colorado, Georgia, Iowa and Kansas.
Across the board, voters have expressed their dissatisfaction with both parties’ inability to co-operate in Congress and the resulting gridlock this has caused.
If the Republicans do win control of the Senate, the day-to-day running of the chamber will become the responsibility of Senate Minority Leader Mitch McConnell, should he win his own tough campaign for re-election.
As the country then shifts its focus to the 2016 presidential election, Barack Obama is likely to find it increasingly hard to operate as his term draws to a close, analysts say.
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