Both teams qualified for the World Cup in style, sit proudly in the top five of the FIFA world rankings and will be among the eight seeds when the draw takes place in Brazil next month.
Brazil coach Luiz Felipe Scolari faces tormentors Honduras, Argentina and Ecuador meet in New Jersey, Italy host Germany in a heavyweight clash in Milan and England play an exciting Chile side at Wembley in matches featuring eight other finalists.
World and European champions Spain continue their games against former colonies on Saturday in Equatorial Guinea, whose team include several players from the Spanish lower leagues.
Altogether, 17 of the 21 teams who have so far made sure of places at next year's finals in Brazil will be in action between Thursday and Saturday with only Iran, Costa Rica, Australia and Bosnia sitting out.
Belgium, blessed with an outstanding generation of talented players such as Eden Hazard and Marouane Fellaini, stormed through their qualifying group, winning eight and drawing two of their 10 games.
They have qualified for the World Cup for the first time since 2002 while Colombia, spearheaded by Radamel Falcao and ably backed by Jackson Martinez and Juan Cuadrado, will end a 16-year absence at the finals.
Former Colombia coach Francisco Maturana, whose team arrived at the 1994 World Cup among the favourites only to go out in the first round, has warned against over-ptimism.
"We've now got a generation that has reached a pretty high standard, with all of the players fighting for trophies in major leagues," he told FIFA.com.
However, he added: "Right now I'd say there's a little bit of uncertainty around the team. Putting results to one side, I think there's been a question mark hanging over Colombia's true potential.
"The world remembers big things like Colombia in 1994. Going into that World Cup we played something like 24 games and won the lot. But then we went and lost the wrong game at the finals."
Italy and Germany, who strolled through their qualifying groups, met barely a year ago in the Euro 2012 semi-finals, with Cesare Prandelli's side winning 2-1.
Mario Balotelli is set to lead Italy's attack on Friday despite a recent loss of form which has also seen the controversial striker twice suspended in Serie A.
Honduras and hosts Brazil last met in a full international in 2001 at the Copa America, where the Central Americans pulled off a shock 2-0 win which left Scolari fighting to keep his job.
'Big Phil' survived and recovered from the humiliation to lead his side to a fifth world title in Japan one year later.
Scolari, who was reappointed a year ago, has recalled Robinho after a two-year absence for the match in Miami.
Argentina will have a chance to test themselves without the injured Lionel Messi against Ecuador in New Jersey on Friday.
England will attempt to score their first goal against Chile since 1953 when they meet the South Americans at Wembley. Chile won 2-0 on their last visit before the 1998 World Cup and the previous two meetings ended in goalless draws.
Chile coach Jorge Sampaoli has maintained the high-tempo, attacking game favoured by Marcelo Bielsa, who led them at the previous World Cup in South Africa.
Netherlands will be without injured striker Robin van Persie when they host Japan in Genk in neighbouring Belgium on Saturday and Switzerland make a long trip to South Korea for two Europe-Asia clashes featuring qualified teams.
Other finalists in action are the United States, who visit Scotland on Friday when Russia will meet Serbia in Dubai having travelled from chilly Moscow.
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- Luiz Felipe Scolari
- FIFA world rankings