Sessions, 70, who has served two decades in the Senate from Alabama, was confirmed by a 52-47 vote largely along party lines after Democrats raised public opposition to his confirmation.
Democrats, civil rights and immigration groups have voiced alarm about Sessions' record of controversial positions on race, immigration and criminal justice reform.
With Sessions as attorney general, eight of President Donald Trump's 22 Cabinet nominees have been confirmed.
Sessions, who is a known immigration hardliner, will take the lead of the Justice Department as its lawyers are defending Trump's temporary entry ban on people from seven predominantly Muslim countries and all refugees, the most controversial executive order of the young administration.
The left-leaning Center for American Progress think tank questioned whether Sessions would be an independent legal voice to challenge Trump's agenda.
"Trump has shown little respect for the courts or the constitutional limits on his power, and there is no reason to think that Attorney General Sessions will act as an independent check on the president," said Michele Jawando, vice president for legal progress at the think tank.
Earlier it was reported that US Senate approved Nikki Haley as UN representative. She will replace Samantha Power, who has been in office since 2013.