The 17-year-old was riding a yellow Kawasaki when it collided with a Vauxhall Insignia at 11pm on Friday night.
Officers now want anyone with information to come forward.
A Hampshire police spokesperson said: “We are appealing for witnesses after a boy died in a collision in Portsmouth.
“Officers were called to James Callaghan Drive just at around 11pm yesterday, 4 July, after a yellow Kawasaki motorbike was in collision with a grey Vauxhall Insignia.
“The rider of the motorbike, a 17-year-old boy from Southampton, was sadly pronounced deceased at the scene.
“Officers are conducting a number of enquiries but are asking the public for any help that may assist our investigation.
“Were you on the road at the time? Perhaps you saw either vehicle in the run up to the collision? Do you have dash cam or CCTV footage?
“Anyone with information is asked to call 101 with reference 44250297331, or submit information via our website: https://www.hampshire.police.uk/tua/tell-us-about/cor/tell-us-about-existing-case-report.”
