The international police agency says the notice was issued at the request of Kenya, where she is wanted on charges of possessing explosives and conspiracy to commit a felony in December 2011.
Lewthwaite, named the world's most wanted woman, was married to one of the suicide bombers who attacked London's transport network in 2005.
She is wanted by Kenyan authorities over alleged involvement in a plot to bomb holiday resorts there.
South African television station ENCA said credit records showed Lewthwaite racked up debts of nearly 30,000 rand ($3,000) to two leading South African banks during her time in the country and owed nearly $1,000 to two clothing stores.
Radio reports said she worked as an IT specialist for a halal pie shop in Lenasia, a south Johannesburg suburb known for its Muslim population.
News media speculated about her possible involvement in last week's attack on a Nairobi mall after a Kenyan minister said a British woman was in the group.
British police have also cited Lewthwaite as a possible suspect.
The current death toll is 72 and is likely to climb with uncounted bodies remaining in the wreckage of the mall.
Another 175 people were injured, including more than 60 who remain in hospital.
At least 18 foreigners were among those killed.
The Interpol notice made no mention of Westgate, however, saying that Lewthwaite is wanted on charges of possessing explosives and conspiracy to commit a felony in December 2011.
It is not clear why the notice has been issued now.
African authorities have linked her to other attacks as well - again, without presenting evidence of her involvement.
She is believed to have been questioned by police once but was not taken into custody.
Circulated to all 190 Interpol member countries, the Red Notice represents one of Interpol’s most powerful tools in tracking international fugitives.
'By requesting an Interpol Red Notice, Kenya has activated a global ‘tripwire’ for this fugitive,' said Interpol Secretary General Ronald K Noble.
'Through the Interpol Red Notice, Kenyan authorities have ensured that all 190 member countries are aware of the danger posed by this woman, not just across the region but also worldwide,' said the Head of Interpol.
Yesterday, British anti-terror officers told a court how a colourful selection of sexy underwear was found at one of the White Widow’s Kenyan safe houses.
Giving evidence at the trial of Samantha Lewthwaite’s accomplice, Jermaine Grant, in Mombasa, Scotland Yard counter-terrorism detective Robert Garrick said police retrieved a collection of pink, black and red lingerie along with the Muslim convert’s birth certificate.
The villa, in the Nyali district of the Indian Ocean resort, was one of five being rented by Lewthwaite, 29, before police foiled her and Grant’s plot to blow up British tourists in December 2011.
Both Lewthwaite and Grant, 29, from Newham, east London, have been charged with planning to cause the loss of lives and possessing bomb-making chemicals.
TUMESHIRIKI NA KUCHAMBUA KUTOKA DM''