Collins, 67, managed to defeat 48-year-old Democrat Susan Gideon, president of the Maine State House of Representatives.
“I feel this is a confirmation of the work I’m doing in Washington, of fighting every day for the people of Maine,” Collins told reporters.
Gideon said he called Collins to acknowledge his defeat.
“I congratulated her on winning this election and said I would always be available to serve the people of Maine,” Gideon said in a Facebook video.
The result is a step back for Democrats, who hope to win at least three seats to gain control of the 100-seat Senate.
Gideon has led most opinion polls since July, arguing that Susan Collins sacrificed her independence to support President Donald Trump.
After counting 75% of the vote, Collins is ahead of Gideon by 49.8% to 43.4% of the vote, according to Edison Research.
Tomorrow has a history of electing moderate Republicans, but the number of politicians like Collins has declined in an era of strong political politics.
Collins has been a senator since 1997, and in 2014 she was re-elected with over 68% of the vote.