Murray River Police District officers are investigating a head-on collision that killed a man and a woman on the Riverina Highway west of Albury on late Wednesday afternoon.

Emergency Services were called to the scene outside Howlong at about 4.45pm on Wednesday after reports of a Toyota Yaris and a Toyota Landcruiser had collided head-on.

"The Yaris driver, a 62-year-old man, and a 54-year-old female passenger died at the scene," a NSW Police statement said.

"A second passenger, an 81-year-old man, was freed after being trapped. He was treated by paramedics and taken to Albury Base Hospital where he remains in a critical condition.

"The Landcruiser driver, a 38-year-old woman, suffered minor injuries and was also taken to Albury Base Hospital."

Police have commenced an investigation into the circumstances surrounding the crash.

A report will be prepared for the Coroner.

PREVIOUSLY:

Two people have been killed in a two-vehicle collision on the Riverina Highway west of Albury on Wednesday evening.

Emergency Services were called to Howlong, 30 km west of Albury at about 4.45pm after reports of a two-vehicle crash.

"The driver and passenger of one vehicle died at the scene. A second passenger has been taken to hospital in a serious condition," a NSW Police Force statement said.

"The driver and sole occupant of the second vehicle suffered minor injuries.

"Officers from Murray River Police District are on scene and have established a crime scene."

Five NSW Ambulance crews and a Toll Rescue helicopter were dispatched to the scene and paramedics treated four people upon arrival.

Two patients died at the scene and an 81-year-old male was treated for head and arm injuries and a 38-year-old female was treated for a minor head injury.

The two injured patients were taken to Albury Base Hospital in a stable condition.

"Attending a scene like this is tragic for everyone. It will stay with first responders, witnesses and the injured for a long time to come," NSW Ambulance Service Inspector Bruce Purves said.

"It's absolutely heartbreaking for the families of the victims, especially just a few days out from Christmas."

"During the holiday period please take extra care on the roads. We want you to get home to your families safe."

The Riverina Highway was closed in both directions as of 7pm on Wednesday around the crash site located between Howlong-Balldale Road and Carrolls Lane, west of Howlong.

Transport for NSW has advised motorists to use diversions, check signage and allow extra travel time

"Ongoing police investigations are expected to take some time," Transport for NSW stated.

"All vehicles in both directions are being diverted via Howlong-Balldale Road d, Walbundrie Road, McGorman Lane, and Hopefield Road.

Police were continuing to investigate the crash on Wednesday evening and have urged anyone with information about the incident to contact Crime Stoppers by phone on 1800 333 000 or online at nsw.crimestoppers.com.au.

Information given to Crime Stoppers is treated in strict confidence.