Police said the two pedestrians were hit at the intersection of Wyllie Rd and Puhinui Rd in Papatoetoe about 7pm.
The road is closed and diversions are in place on Puhinui Rd at Noel Burnside Rd and Vision Place, and on Wyllie Rd at Gifford Rd.
Motorists are being asked to avoid the area.
A witness at the scene told the Herald the bodies of two people, which had been covered with a white sheet, lay in the middle of the road.
The bus was parked up on the side of the road also.
"It looks like the bus has collected these people and now two are dead."
A man who lives nearby, Avin Prasad, said the bus involved was the number 380, a bright orange bus that travels to Auckland Airport and is also known as "The Airporter".
Prasad said he did not see the pedestrians, but steaming takeaway food was on the side of the road at the scene.
A large crowd of people were at the scene and it was difficult to see much.
A police cordon had been put up and the route heading towards the motorway had been blocked off.
Four ambulance vehicle could be seen at one point, the witness said, and the Police Serious Crash Unit was also in attendance.
"There may be family members here as there is a lot of wailing right now.
"A lot of people have come out."
It appeared the bus was turning into Wyllie Rd when the incident occurred.
A worker at a nearby Mobil service station said he could see the crash on his security cameras and "it's serious".
The worker said he could see emergency vehicles and crowds.
"It's too big ... [it looks] like a marathon. There's too many vehicles [stopped]."
A man working at the Chinese Choice Takeaways said a customer told him a bus had struck two men.
There were "heaps" of ambulances and police cars, he said.
