Police closed the A61 after a white Ford Transit van came off the road at around 9.50am.
The van appears to have hit a number of road signs before crashing into a tree on the stretch of road near The Grammar School at Leeds site.
A West Yorkshire Police spokesman said that the male driver had been taken to Leeds General Infirmary by ambulance, where he remained in a serious condition.
The road had been closed in both directions between the school and Wike Lane until around 2pm.
Coastliner buses and Harrogate Bus Company's 36 service were disrupted earlier as a result of the road closure.