Motorists hitting the roads on Sunday faced a major traffic migraine after a crash forced the closure of Mitchell Freeway.

A serious crash on the major thoroughfare resulted in all southbound lanes being shut at Roe Street in West Perth for more than six hours.

WA Police confirmed a 36-year-old male driver was driving southbound when he lost control and smashed into a concrete barrier about 4.20am on Sunday.

Both the driver and his 37-year-old female passenger suffered serious injuries.

Main Roads had first reported the major Perth road as closed shortly after 6.15am.

Emergency services and incident response both attended the scene, with the pair taken by ambulance to hospital.

The freeway had remained shut to all motorists heading southbound throughout Sunday, with Main Roads reopening the thoroughfare shortly before 12.30pm.

Traffic remains heavy through the area, with motorists warned that delays stretch back to Vincent Road.