The police helicopter was called to Billingshurst following a serious crash just outside the village.
Emergency services have closed part of the A29 Stane Street in Adversane after car left the road and collided with concrete bollards near the junction with Adversane Lane.
Police said a woman was seriously injured in the crash.
Two people made off from the scene and officers along with the police helicopter have been scouring the area in an attempt to find the pair.
An eyewitness has told the County Times the police helicopter was circling over the Weald School.
Several other police cars have been seen patrolling the village along with police dog units, the eyewitness added.
Road closures remain in place in the area and severe delays are being reported.
Anyone with any information is asked to call 101 quoting operation Arunside.
A large police presence including around five police cars were also spotted in Forge Way in Billingshurst. It has not yet been confirmed whether this is related to the incident.