The pair, believed to be father and daughter, had just picked up a car in Beaufort and were towing it on a trailer back toward their home when the accident occurred.

Police said the pair had not travelled far when the ute they were driving in collided head on with a truck near the railway overpass.

The truck driver, a male in his 40s, was transported to Ballarat Base Hospital with leg injuries and shock.

Senior Sergeant Stacey Glenister appealed for any witnesses to come forward and help police piece together the circumstances surrounding the accident.

“If any witnesses could contact Crimestoppers, that information will get fed through to investigators,” she said.

The highway was closed in both directions after the accident occurred soon after 9.30am, and was not reopened until investigators finished their work around 5.30pm,

“We’ve had a ute towing a trailer and that collided head-on with a truck and we've lost a man and a woman in that crash,” said Victoria Police Assistant Commissioner Doug Fryer at a press conference confirming the accident.

“The amount of trauma we’re experiencing in the country at the moment is just significant.”

The two occupants of the car died at the scene.

The Beaufort crash was one of several horror incidents on the state’s roads over the weekend.

Three people died following a crash in Lakes Entrance just hours before the Beaufort accident, and a 43-year-old Jamieson man died in a hit-run incident in Jamieson early on Sunday.

The weekend deaths bring the state’s road toll to 225, 35 less than at the same time last year.

Police also responded to a minor accident at the corner of Creswick Road and the Western Highway – the scene of a fatal accident earlier this month – on Saturday afternoon.

Racegoers heading to the Ballarat Cup collided with another vehicle at the intersection. Occupants from both cars sustained only minor injuries and did not require medical attention.