Thalang Police were notified of the accident, opposite the Esso petrol station next to Wat Srisoonthorn on Thepkrasattri Rd southbound, at 3:30am.
Police and rescue workers from Srisoonthorn Municipality arrived to find a Phuket-registered Honda Wave 125i motorbike with heavy damage to its rear.
Nearby on the road were two people, a man and a woman, who had suffered serious injuries.
The woman, Chanidapa Saetan, 38, from Bangkok, was the driver of the motorbike. She had suffered severe injuries and rescue workers had to perform CPR at the scene.
The man, later identified as Somtam Kerdthong, 43, was the passenger. He was injured but still conscious.
Both Ms Chanidapa and Mr Somtam were urgently rushed to Thalang Hospital.
Their latest condition has yet to be reported.
Police found a part from a black car at the scene believed to be involved in the collision.
Officers recovered the part as evidence while they continue their investigation and start their hunt for the driver.