The sign, which reads "Arbeit macht frei", or "Work will set you free", was stolen early this morning, according to a spokesman for the camp, which is now a museum.
"It's a profanation of the place where more than a million people were murdered. It's shameful," he said.
"Whoever did it must have known what he was stealing and how to do it."
The forged iron inscription was not hard to unhook from above the large gates at the entrance, "but you needed to know how," he said.
The police have launched an inquiry and the local governor has promised his full support.
Police spokesman Malgorzata Jureck told public radio station Trojka that the theft had taken place around 6am local time.
"A police dog has been set on the trail of the thieves," she added.
The site of Auschwitz-Birkenau, in southern Poland, is closed at night and patrolled by nightwatchmen.
Police were looking at video surveillance footage from the site Friday. Mensfeld this was the first serious case of theft at the site.
Around 1.1 million people perished at Auschwitz-Birkenau – one million of them Jews from Poland and elsewhere in Nazi-occupied Europe – some from overwork, starvation and disease, but most in the notorious gas chambers.
It was one of six death camps set up in Poland – home to pre-war Europe's largest Jewish community – by the occupying Germans, who murdered six million Jews during the war.