The girl was walking with a friend into the city's Witton train station on Tuesday evening when a man approached her, led to her to a secluded area of the station, and raped her, police said.
Shortly after the attack, the girl left the area and flagged down a passing car to ask for help. When she got into the vehicle she was sexually assaulted for a second time by another man, police believe.
The girl, whose age was initially given by police as 15, reported the attacks to police when she got home.
The two men detained Saturday, one aged 35 and the other 27, are both from the Birmingham area, British Transport Police said. They are being held in police custody on suspicion of rape.
Both the arrests relate to the first incident at Witton station, police said.
Detective Chief Inspector Tony Fitzpatrick of the British Transport Police said there had been significant developments in the case overnight after police released CCTV footage.
Police continue to appeal for information regarding the second rape in a vehicle in the early hours of Wednesday.
Fitzpatrick said previously that specialist officers were supporting the victim after what he called a "horrifying ordeal."
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