Police said the 27-year-old goalkeeper was killed late Sunday after burglars broke into the house of his pop-star girlfriend Kelly Khumalo, making off with a cell phone.
South Africa's president led a shocked nation in voicing outrage at the attack.
More than 17,000 people were killed in South Africa last year, but the slaying of a popular sporting hero has stunned even this crime-weary nation.
"Words cannot express the nation's shock at this loss," said President Jacob Zuma.
Zuma said police must "leave no stone unturned in finding his killers" and bringing them to justice.
National Police Commissioner Riah Phiyega said a manhunt was now under way.
"We believe that someone, somewhere, somehow knows something about this crime," she said, appealing to the public to come forward.
Police have offered an increased reward of 250,000 rand ($23,000) for any information leading to his killer's arrest.
Fighting back a flood of tears, national football coach Shakes Mashaba described Meyiwa as a "very kind person" who was the first name on his teamsheet.
Team-mates at his local club Orlando Pirates were sobbing and crying uncontrollably during a Monday team meeting, according to club officials.
Tributes to Meyiwa flooded in from across the football world.
Spain's World Cup winning goalkeeper and captain Iker Casillas posted on his Instagram account a picture of Meyiwa after the pair had swapped jerseys, saying "Very sad for the dramatic loss of friend RIP Senzo."
FIFA president Sepp Blatter described Meyiwa's killing as a "senseless, tragic loss".
Meyiwa's South African team-mate, Doncaster Rovers-based Dean Furman, said he was "beyond devastated at the loss of our captain and friend".
It is just latest tragedy to befall South Africa's sporting fraternity.
They country is still reeling from the death of former world 800-metre champion Mbulaeni Mulaudzi in a car crash on Friday and the jailing of fallen Paralympic hero Oscar Pistorius for the killing of his girlfriend last year.
- 'Undesirable for our country ' -
Phiyega said that with the eyes of the world again on South Africa's high crime rate, a task team had been appointed to quickly to close the case.
"This type of loss is undesirable for our country, this type of loss does not augur well for our brand and image out there."
But Phiyega rejected accusations that Meyiwa's killing was being treated differently because of the victim's high profile.
Meyiwa was gunned down at a house in Vosloorus, a township about 30 kilometres (20 miles) south of Johannesburg at around 8 pm (1800 GMT) on Sunday.
"It is alleged that two suspects entered the house and confronted the occupants, while a third suspect was outside," said Phiyega.
After an altercation "a shot was fired, the goalkeeper was hit in the upper body and was taken to hospital, where he was declared dead on arrival".
One cell phone was taken and the three suspects, describe as being in their late 20s and early 30s, fled on foot.
- Into the limelight -
After many years in the South African football shadows, Meyiwa had a meteoric climb to fame with the Orlando Pirates.
He displaced national squad goalkeeper Moeneeb Josephs as first-choice at Pirates, the only South African side to be crowned African champions.
And a recent injury to South Africa captain and goalkeeper Itumeleng Khune gave Meyiwa a chance in the national team, popularly known as Bafana Bafana (The Boys).
New national coach Mashaba not only promoted Durban-born Meyiwa to replace Khune but also made him captain of a team that have been in the doldrums for some years.
Meyiwa responded to his promotion by leading the team to victories over Sudan and Congo Brazzaville and draws with Congo Brazzaville and Nigeria, a country South Africa traditionally struggle against.
He did not concede a goal in the four matches and if South Africa defeat Sudan in eastern city Nelspruit next month they will qualify for the 2015 Africa Cup of Nations tournament.
Meyiwa is due to be buried near Durban on Saturday.
South Africa's biggest football spectacle -- a Soweto derby between Orlando Pirates and Kaizer Chiefs for this weekend has been cancelled.