Emergency services were called to the A16 at Louth at 10.51am following reports that a silver Citroen car and a silver Triumph motorcycle had collided.
The incident happened just north of the A57 roundabout, close to the layby near Coxey Hills on the northbound carriageway.
The rider of the motorcycle received medical assistance at the scene before being taken to hospital for further treatment, where he remains in a serious condition. His next of kin have been informed.
The driver and passenger in the car are not believed to have suffered any injuries.
Road closures have been put in place while police carry out our enquiries, and are expected to remain until later today, so please avoid the area.
Officers are now appealing for any witnesses to the incident to come forward.
A Lincolnshire Police spokesman said: “We are keeping an open mind about the circumstances of the incident while we carry out our investigation.
"We are keen to ask the public for help and would appeal for any witnesses we have not yet spoken with to come forward.
“We are also keen to view any dashcam footage of the collision or either vehicle prior to the incident.”
If anyone has any information relating to the collision, contact Lincolnshire Police by calling 101 quoting incident number 112 of 8 October, or emailing [email protected] .
Alternatively, you can report via the independent charity CrimeStoppers on 0800 555 111 or online at https://crimestoppers-uk.org/.