This is one time where a historic trail marker really does mark the historic route that it's commemorating. The Santa Fe Trail dated to 1821. It began in Franklin, Missouri, proceeded to Independence and Westport, and thence from Missouri to Santa Fe, New Mexico, which was then Mexican territory.
This sign is on Missouri 41 at the entrance to the Arrow Rock Historic State Site, with numerous historic buildings from the 19th century in the Saline County village of Arrow Rock. At one time, the route into Arrow Rock from Missouri 41 may have been marked as Spur Route 41. It is still shown as a spur route on MoDOT county maps, though it is not marked in the town.