The drive from Madrid to San Sebastian de Garabandal is approximately 250 miles (400 kilometers) and typically takes between 4 and 5 hours.

Directions
Take route N1 (also designated as E05) North toward Burgos
This portion of the trip will take about 2 hours.

In Burgos, continue straight onto route 623 North toward Santander
Continue on 623 for about 2 hours until route 634 West toward Oviedo.

You will be on this road for about 20 - 30 minutes until the town of Cabezon.
In Cabezon, turn left onto 625 toward Reinosa. Continue on this road for another 20 minutes or so until you see a sign signaling a right turn toward the town of Carmona. Take that right (note that there is a bar called "LUKY" on the corner where you must turn right).

Follow the road to Carmona then continue straight to the town of Puentenansa.
In Puentenansa take a left (designated by a sign) toward the town of Cosio. Follow through and in Cosio take a right (designated by a sign) toward San Sebastian de Garabandal. Follow the road and you are there.

All of the turns and route numbers are clearly signed.

These directions, while accurate, are best used in conjunction with a detailed roadmap. One map that we have found quite helpful is the Euro Travel Atlas of Spain and Portugal by American Map. This book is available at most bookstores including online from Amazon.com.