Police have confirmed the crash at Tallygaroopna this afternoon was a fatal one.
Major Collision Investigation Unit detectives are investigating the circumstances surrounding the incident.
Investigators have been told two vehicles collided near the intersection of the Goulburn Valley Hwy and Victoria St about 3.15pm.
The driver of one of the vehicles died at the scene and is yet to be formally identified.
The driver of the second vehicle was airlifted to hospital with non-life-threatening injuries.
The circumstances surrounding the collision are yet to be established and the investigation is ongoing.
The northbound lane detour has been moved south to Katamatite-Shepparton Rd, from its earlier position at Zeerust Rd.
EARLIER, 4.30pm:
The main road through Greater Shepparton is closed in both directions this afternoon.
Police on the scene have confirmed that a crash at Tallygaroopna is the cause of the closure of the Goulburn Valley Hwy.
Ambulance Victoria confirmed that paramedics were called to the incident at around 3.10pm on Wednesday, September 13.
A man believed to be in his 30s is being treated for a lower-body injury and is in a stable condition.
An air ambulance has been dispatched.
Ambulance Victoria confirmed at least one other person was involved in the crash.
The northbound lane of the Goulburn Valley Hwy is closed at Zeerust Rd, with a detour in place.
The southbound lane is closed at Victoria St, the turn-off to Tallygaroopna.
Emergency services are on the scene, with the section of highway expected to be closed for some time.