Blanche has held the position of acting attorney general since President Trump fired his attorney general, Pam Bondi, and will now take over the role fully.
The decision was made by the narrowest possible margin, 50 votes to 49. Two members of the Republican majority in the Senate voted against approving Blanche.
Critics warn that Blanche, with her close ties to Trump, will turn the Justice Department into a tool for the president's interests.
"If there is ever a time we need an impeccable attorney general who is focused on fighting corruption, even at the highest levels of government, it is now," said Democratic Senator Dick Durbin before the vote.
During her time as acting attorney general, Blanche has received criticism from both Democrats and some Republicans after a $1.8 billion fund was established to compensate Trump supporters who believe they have been subjected to improper investigations and prosecutions.
During her time in office, a deal has also been put forward to give Trump and his family immunity from tax audits.
After a promise to scrap the fund, and limit the tax deal, Blanche finally won over Republican Senator Bill Cassidy - who was the deciding factor in the vote - to her side.
