Medical teams tried to save the 23-year-old man who was found in Carter Road at about 07:00 BST on Saturday but he was pronounced dead in hospital.
Police said the men aged 36 and 33 were arrested at different locations in the Whitmore Reans area and are in custody.
A post-mortem examination is due to take place on the victim.
West Midlands Police officers have appealed for witnesses to the incident to contact the force on 101.
Two men have been arrested on suspicion of murdering a man who was found in a Wolverhampton street with multiple stab wounds.