South African Breweries has agreed a £3.8bn deal to take over Miller, the US brewer owned by tobacco giant Philip Morris.
It has also given its strongest hint to date that it is considering a bid for the UK's biggest brewer Scottish & Newcastle (S&N).
The latest deal means newly-created SABMiller is the second biggest brewing group in the world, behind Anheuser-Busch.
It is now hoped SAB can turn Miller around after 10 years of under-performing in the US market.
Graham Mackay, chief executive of South African Breweries said: "This transaction represents a new chapter in our development, taking SABMiller to the number two position globally and positioning it to be a major participant in the on-going consolidation of the global beer industry."
John D Bowlin, president and chief executive officer of Miller Brewing, said: "Everyone wins through this dynamic combination, including Miller's employees, customers and distributors.
"We are combining two great brewers with distinct, yet complementary assets and talents with the promise to become greater than the sum of its parts."
According to The Times, Mr Mackay was questioned over whether the Miller deal made a bid for S&N more or less likely.
He said: "We never comment on individual companies but this deal is absolutely neutral as far as S&N is concerned. It says neither yes nor no on S&N."
Tobacco group Philip Morris, which has owned Miller since 1970, will receive 430 million shares in the new company and has agreed not to sell any shares until June 2005.
SAB closes in on $5bn Miller (20 May 2002)
SAB confirms talks to buy Miller (5 April 2002)
SAB eyes US brewer Miller (18 March 2002)