The Republicans have won Senate seats in Arkansas, Colorado, Iowa, Montana, North Carolina, South Dakota and West Virginia, which were earlier held by the Democrats.
In the US state of Kentucky, Senate Republican leader Mitch McConnell defeated Democratic challenger Alison Lundergan Grimes. In January, he is set to become the majority leader in the Senate.
Overall, 36 of the 100 Senate seats were at stake Tuesday. Until now, the Democrats had 53 seats while the Republicans had 45 seats, and two seats belonged to independent senators.
The results of the elections mean that the new Congress, which is due to convene in January, will be fully controlled by the Republicans, who will head all the committees in both houses and define the legislative agenda.
Such a prospect will create serious difficulties for US President Barack Obama during the next two years of his presidency.