The raid, which the state broadcaster said resulted in two arrests including one Gupta family member, came amid reports Zuma was preparing to tell South Africa he was stepping down after nine years in office dogged by scandal and economic stagnation.
Finance Minister Malusi Gigaba said Zuma would speak at 0800 GMT and satellite trucks were in position at Pretoria's Union Buildings, the seat of the country's government. Zuma's office said there was no "official communication" of any impending address but urged media to wait.
A dozen officers from the elite Hawks police unit sealed off a street leading to the Gupta home in Johannesburg's upscale Saxonwold suburb. One officer blocked access to Reuters, saying: "This is a crime scene."
Minutes later, an unmarked police van left the compound as residents applauded police officers and hurled abuse at security guards for the Guptas, who have been accused by South Africa's top anti-corruption watchdog of influence-peddling and swaying the appointment of cabinet ministers.
"Finally something is being done about it. These guys must get out of our country. They must leave us alone. They have done enough damage," said Tessa Turvey, head of the local residents' association, standing outside.
On Tuesday, the ruling African National Congress (ANC) ordered Zuma to step down as president of the country, giving him no firm deadline but saying the party was sure he would comply and "respond" on Wednesday.
Zuma and the Guptas - a family of wealthy Indian-born businessmen - deny any wrongdoing.
A lawyer for the Gupta family said he could not comment on the raid because he had yet to see the search warrant.
"We're not playing around in terms of making sure that those who are responsible in the so-called state capture, they take responsibility for it," Mulaudzi said.
Signs of law enforcement mobilising against the Guptas - and by association Zuma - caused the rand to strengthen 0.5 percent against the dollar. The currency has tended to gain ground on any sign of Zuma's political departure approaching.
So far there has been silence from Zuma in response to Tuesday's ANC order, suggesting a power struggle behind the scenes with new party leader Cyril Ramaphosa.
Besides his controversial relationship with the Guptas, Zuma has 783 counts of corruption outstanding against him relating to a multi-billion dollar state arms deal in the late 1990s.
Zuma's spokesman could not be reached for comment.
Besides the pressure from the ANC, Zuma is facing a no-confidence motion in parliament brought by the opposition Economic Freedom Fighters and set for Feb. 22.
The ANC could throw its weight behind such a vote if Zuma, who has survived several no-confidence motions in the past, refused to resign. The entire Cabinet would have to step down if such a vote went through.
(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)