Generally speaking, the native people were not able to resist the Spanish colonization of North America. They have certainly tried. The native source states that the Aztecs waged war against Cortés with all their force to avenge the massacre in the Main Temple. They could achieve temporary successes, such as driving Cortés and his entourage from Tenochtitlan during the Night of Sorrows. However, these successes were not lasting, and the eventual outcome of the armed struggle was in Spanish favor.
The reason why the native population proved unable to resist the Spanish advances was twofold. To begin with, the colonizers possessed an overwhelming superiority in military technology. While the Aztecs’ beast weapons were bows and wooden clubs, sometimes with obsidian blades, the Spanish brandished firearms and metal swords. Moreover, the colonizers also had horses and, thus, cavalry, which could be deadly to the natives who had no skills at defending against charging riders. Apart from that, the native polities were usually deeply divided, which allowed the colonizers to enlist native allies in considerable numbers.
While Cortez’s Spanish force in his wars against the Aztec empire numbered hundreds at best, there were thousands of native allies fighting on his side. Thus, it was not only the Spanish whom the resisting natives had to face but many of their local neighbors as well. Between the fearsome military technology of the former and the numbers of the latter, any organized resistance had little chance of succeeding.