Republican Bernie Moreno has won the Ohio Senate race, defeating Senator Sherrod Brown. The GOP managed to flip two seats, reversing the 51-to-49 majority held by Democrats.
Battleground races in Montana, Arizona, Nevada, Pennsylvania, Michigan and Wisconsin remained uncalled.
Republicans stood to gain more seats given very tight races in Wisconsin, Pennsylvania and Michigan.
It is a major victory for Republicans and a serious blow to Democrats’ efforts to maintain their majority in the Senate.
Control over the House of Representatives is still up for grabs, with over 100 seats yet to be called. Currently, Republicans control the chamber with a narrow margin.
If they prevail, Republicans would be in a position to dictate the agenda in Washington, helping Trump deliver on his promise to slash taxes and restrict immigration.
The final result will probably not be known for days, but Tuesday's results ensured Republicans in the Senate would be able to help Trump appoint conservative judges and other government personnel.
Republicans stood a chance to widen their Senate majority further, as their candidates were leading Democratic incumbents in Michigan, Montana, Pennsylvania, Nevada and Wisconsin.
Republican incumbents also held off challengers in Texas, where Ted Cruz won reelection, and Nebraska, where Deb Fischer defeated independent Dan Osborn.

Kuwait foils terror plot targeting state leaders
Iran rejects Trump's talk of negotiation as Israel and Iran launch airstrikes
Cyprus has opened discussion with UK over its bases, president says
Netanyahu seeks to avoid snap vote as Iran war gives no boost in polls
Luxury Paris hotel near Elysee reopens after fire forces brief closure
Germany renews push for sugar tax and energy drinks ban for children
No injuries reported as drone attack hits fuel tank at Kuwait's airport
US expected to send thousands more soldiers to Middle East
