The singer broke her long-held silence on politics in October when she endorsed Phil Bredesen, a former governor of the state.
"In the past I’ve been reluctant to publicly voice my political opinions but due to several events in my life and in the world in the past two years, I feel very differently about that now," Swift wrote in an Instagram post, written almost a month before the elections.
Swift said that the Republican's voting record on issues such as LGBT+ rights "appals and terrifies me", adding she would like to support women in office but "I cannot support" Ms Blackburn.
Swift faired better with her endorsement of Jim Cooper, a Nashville Democrat who defeated his Republican challenger to return to the House of Representatives.
Voter registration spiked following the singer's intervention but Ms Blackburn, a staunch conservative, took the Senate seat on Tuesday.
She is the first woman to represent the southern US state in the Senate.
Ms Blackburn's win is not a surprise, with Tennessee long considered a safe Republican seat.
The state has voted for GOP candidates in presidential elections since 2000.
In 2016, 60 per cent of voters in Tennessee supported Donald Trump.
As the result in Tennessee became clear, Laura Ingraham, a right-wing anchor at Fox News, tweeted "hey taylorswift13, haters gonna hate. #shakeitoff".
Additional reporting by agencies
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