85-year-old pope who abruptly cut short his pontificate by declaring he was too weak in body and mind to keep up with the modern world.
The Vatican says 50,000 people have obtained tickets for the event but many more may come and city authorities are preparing for 200,000, installing metal detectors in the area, deploying snipers and setting up field clinics.
No parking has been allowed in the zone since 10:00 pm Tuesday, and cars were to be barred entirely from 7:00 am on Wednesday.
The weekly audience, which is exceptionally being held in St Peter's Square because of the numbers expected, is to begin at around 10:30 am (0930 GMT) and usually lasts around an hour with a mixture of prayers and religious instruction from the pope.
Benedict will be the first pope to step down since the Middle Ages -- a break with Catholic tradition that has worried conservatives but kindled the hopes of Catholics around the world who want a breath of new life in the Church.
Rome has been gripped by speculation over what prompted Benedict to resign and who the leading candidates might be to replace him.
Rumours and counter-rumours in the Italian media suggest cut-throat behind-the-scenes lobbying, prompting the Vatican to condemn what it has called "unacceptable pressure" to influence the papal election.
Campaign groups have also lobbied the Vatican to exclude two cardinals accused of covering up child sex abuse from the upcoming election conclave.
The Vatican has said Benedict will receive the title of "Roman pontiff emeritus" and can still be addressed as "Your Holiness" and wear the white papal cassock after he officially steps down at 1900 GMT on Thursday.
Just before that time, the Vatican said Benedict will be whisked off by helicopter to the papal summer residence of Castel Gandolfo near Rome where he will begin a life out of the public eye.
Benedict will wave from the residence's balcony one last time before retreating to a private chapel and, as he has said, a life "hidden from the world".
On the hour he formally loses his powers as sovereign pontiff, the liveried Swiss Guard that traditionally protects popes will leave the residence.
The shock of the resignation and its unprecedented nature in the Church's modern history has left the Vatican sometimes struggling to explain the implications and Benedict's future status -- from the banal to the theological.
Some Catholics find it hard to come to terms with the idea that someone who was elected in a supposedly divinely inspired vote could simply resign.
The Vatican has said Benedict will lose his power of divine infallibility -- a sort of supreme authority in doctrinal matters -- as soon as he steps down.
The Vatican has also explained that the personalised gold Fisherman's Ring traditionally used to seal papal documents -- a key symbol of the office -- will be destroyed by a special cardinal, as is customary in Catholic tradition.
Benedict has also chosen to swap his trademark red shoes for a brown pair given to him by artisans in Mexico during a trip last year.
Starting next week, cardinals from around the world will begin a series of meetings to decide what the priorities for the Catholic Church should be, set a start date for the conclave and consider possible candidates for pope.
The conclave -- a centuries-old tradition with an elaborate ritual -- is supposed to be held within 15 to 20 days of the death of the pope, but Benedict has given special dispensation for the cardinals to bring that date forward.
Cardinals have been flying in from around the world including US prelate Roger Mahony, a former archbishop of Los Angeles stripped of all church duties for mishandling and covering up sex abuse claims against dozens of priests.
A total of 115 "cardinal electors" are scheduled to take part after another voter, British cardinal Keith O'Brien said he would not be taking part after allegations emerged that he made unwanted advances towards priests in the 1980s.