Police officers, supported by firearms teams, responded to multiple calls reporting a shooting on Ruskin Road at 7.50pm on Sunday.
Less than an hour after the 999 calls, officers tracked down and arrested a 38-year-old man and a 39-year-old women on suspicion of attempted murder.
Both are from Wolverhampton and remain in custody.
Before police arrived at the scene, two men had turned up separately at New Cross hospital with serious injuries.
A 41-year-old man had a gunshot wound to the face and a 39-year-old man had knife injuries to the head.
Both remain in hospital.
Police say inquiries are ongoing to understand the motive for the attack.
Ruskin Road, including a shop which the man who was shot ran into, was closed off on Monday while forensic teams carried out searches.
The shooting has left nearby residents worried, with children often seen using the shop near the attack.
Police have spoken to people in the area and have started to identify CCTV and doorbell footage that may have captured the attack.
Anyone with information that could help find the people responsible is asked to send police a message via live chat at west-midlands.police.uk, quoting investigation number 20/445772/22.
Alternatively, call Crimestoppers on 0800 555 111.