Blanche won confirmation in a 50-49 vote on Saturday, with Republican senators Susan Collins and Lisa Murkowski opposing him.
Senator Bill Cassidy was the deciding vote after announcing on Friday he thought Blanche was the best option Trump would put forward.
Blanche had been elevated to the top Justice Department post in an acting capacity after Trump fired Pam Bondi in April.
The vote was the culmination of a weeks-long stand-off between Senate Republicans and the Trump administration over Blanche, who has served as acting attorney-general since April and previously ran day-to-day Justice Department operations as its second-ranking official.
Republican senators had raised concerns about Blanche's handling of the release of Jeffrey Epstein-related documents, as well as his role in establishing Trump's $US1.8 billion ($A2.6 billion) "anti-weaponisation" fund and a related tax-immunity agreement for Trump and his sons.
But Blanche overcame those challenges in frantic meetings around Capitol Hill in the past several weeks, ultimately agreeing in writing to narrow the tax-immunity agreement and end the "weaponisation" payments, which critics have called a slush fund for Trump's allies, including those who rioted at the Capitol on January 6, 2021.
Both the tax-immunity agreement, which barred the IRS from auditing previous tax returns of Trump, his sons and their family business, and the fund emerged from Trump's $US10 billion lawsuit against the Internal Revenue Service.
Questions remain, though, about whether that commitment is legally binding, and whether Trump, who has said he loves the idea of the fund, could later press Blanche, his former personal lawyer, to revive a similar program under another name.
That concern was central to the last two Republican senators Blanche needed to convince - Bill Cassidy and Lisa Murkowski - both of whom met with Blanche on Wednesday after signalling they had not yet decided how they would vote.
Murkowski had cited her lack of confidence in Blanche to "check the worst impulses of this administration".
Cassidy criticised Blanche's role in settling Trump's IRS lawsuit, but said he ultimately trusted Blanche to give the president candid legal advice.
Blanche will take the helm of a Justice Department that has undergone significant change in the first year and a half of Trump's second term.
Under Blanche's leadership, the department has sought prosecutions of Trump's perceived enemies, caused the mass departures of career prosecutors and stated that it served at the direction of the president, a break with longstanding norms of independence.
Federal judges have on multiple occasions criticised prosecutors for bringing what they described as weak cases, and grand juries have declined to indict in some instances.
Blanche has argued that he has helped bring crime to record lows and righted what he says are wrongs brought by the Biden administration against Trump and his conservative allies.
with AP
