Lowy migrated to Australia after World War II, starting out delivering small goods. In 1953 he met fellow immigrant John Saunders (born Jenö Schwarcz). The pair became business partners, eventually creating Westfield (Saunders left the company in 1987). Business Review Weekly measured Lowy's wealth in 2005 at $A4.8 billion, making him Australia's second richest person, behind the late Kerry Packer on A$6.9bn and ahead of Richard Pratt on A$4.7bn.

In May 2001, Westfield paid $US127 million for a 99-year lease on the retail area beneath the World Trade Centre. In September 2003 it was a party to a $US3 billion insurance claim following the terrorist attack on the twin towers. On February 18, 2006, the Los Angeles Times reported that Westfield, "the largest owner of shopping centres in California and the world", had agreed to acquire 15 stores from Federated Department Stores, all but three in southern California.

In 2003 Frank Lowy set up the Lowy Institute for International Policy, an international policy think tank devoted to foreign affairs.

Lowy has become involved with the newly created Football Federation Australia, which has replaced the now defunct Soccer Australia. Many observers credit him and John O'Neill, a former rugby union executive, with resurrecting football (soccer) in Australia. A well structured A-League is now in place, and the country has become a member of the Asian Football Confederation. In addition, the league appointed Guus Hiddink as national coach, with great success: Australia has reached the 2006 FIFA World Cup in Germany.

Lowy is a board member of the Reserve Bank of Australia and has been awarded a Companion of the Order of Australia.