Police responded to an incident on a street off the road leading to Tower Bridge at around 2.35am on Friday.
Officers and London Ambulance staff found a man in his 30s critically injured on Queen Elizabeth Street.
The man was transported to the hospital but was pronounced dead upon arrival.
Officers from the Metropolitan Police's Homicide and Major Crime Command are continuing their investigations and the next of kin have been informed.
A post-mortem will be held to determine the cause of death.
The two men that were arrested remain in custody at separate London police stations.
Tower Bridge was closed following the incident, but reopened at around 9am on Saturday.
Detective Chief Inspector Rebecca Reeves, said: "Although we are in the early stages of the investigation we believe that an argument involving a number of men and women took place in Tower Bridge Road. This then continued in Queen Elizabeth Street where the victim subsequently died.
"The area around Tooley Street has a popular nightlife and I would ask that anyone who had been to a club in the area and may have witnessed the assault to contact us."
Anyone with information is asked to contact the incident room on 020 8721 4868, or Crimestoppers anonymously on 0800 555 111.