The purpose of this study was to examine the effect of technology support, teachers’ confidence in using technology, their beliefs about using technology, and their perceived skills on the use of instructional and application software. The data we used were from 1335 K-12 teachers involved in the Technology Uses and Perceptions Survey (TUPS) study. Teachers were located in 40 different institutions across the state of Florida. According to the findings of this study, the most significant factor in the instructional and application software use of teachers was found as perceived technology skills. Therefore, professional development for perceived skills or technology competencies of teachers might contribute to increasing the instructional or application software use of teachers. In terms of confidence and comfort using technology, they both had direct and positive effects on instructional and application software. Also, the total effect of support from technology specialists for instructional software use is more than application software use. As evidenced by the models developed in this research, teachers’ perceived technology skills for instructional and application software use directly and positively affected their beliefs on usefulness. Our effort to provide more emphasis on the combined effect of a collective set of factors to explain teacher use of technology leads us to address the gaps in the literature on technology use (i.e., the effect of demographic factors and technology availability).