Sydney Harbour Bridge crash kills driver

A horrific head-on crash that closed the Sydney Harbour Bridge for three hours during morning peak has left a woman dead and four others injured, one critically.

The collision triggered widespread traffic chaos and a complicated rescue mission for emergency service workers called to the impact site on the southern side of The Coathanger around 7am.

A helicopter ambulance landed on site to take the injured to hospital and crews from The Rocks Fire Station had to make their way on foot through traffic to the wreckage.

The woman, thought to be in her mid-30s and driving a Mitsubishi Mirage, died at the scene.

Police believe she may have veered across two lanes of traffic into what she mistakenly believed was a northbound lane before colliding with a southbound BMW.

"It was peak hour, extremely heavy traffic ... it does appear one lane had lighter traffic in it and they've crossed into that, perhaps thinking that there was a clear lane of traffic heading in the right direction," Acting Superintendent Paul Dunstan told reporters.

"But I must admit it's way too early to commit to any (of that)."

Supt Dunstan said the lanes on the bridge were clearly demarcated.

A male passenger in the Mitsubishi suffered head and facial injuries and was taken to Royal North Shore Hospital in a critical condition, NSW Ambulance said.

Two other men were also taken to Royal North Shore Hospital with minor injuries.

The severely injured other driver was trapped in her BMW for more than 30 minutes, until rescue crews cut the roof off her car.

NSW Ambulance chief superintendent Cameron Edgar, who was on scene, said it was a difficult job given the location of the wrecks, which were strewn across multiple lanes.

"The lady (BMW driver) ... was conscious throughout. She was obviously concerned and in pain but she was, all things given, in reasonably good spirits," he told reporters.

NSW Ambulance duty operations manager Lucky Phrachanh said paramedics were shocked by what they saw.

"It was a horrific scene to encounter this morning ... paramedics and emergency services never want to attend these types of accidents," Mr Phrachanh said.

Traffic was backed up for hours in all directions with commuters advised to take the train or harbour tunnel, or work from home.