Spanish colonization of the Americas began with the "discovery" of America by Chistopher Columbus in 1492.
In 1720 a small expedition from Santa Fe met and attempted to parley with French allied Pawnee in what is now Nebraska. Things did not go well and a battle ensued; the Spanish were badly defeated, only 13 managing to return to New Mexico. Although this was a small engagement it is significant being the furthest penetration of the Spanish into the great plains setting the limit to Spanish expanision and influence there.