Moodle is an open-source learning management system that is widely used today, especially in higher education settings. Although its technological acceptance by undergraduate students has been extensively studied in the past, very little is known about its acceptance by university professors. In particular, as far as we know, the literature contains no previous experiences related to South American teachers. This paper aims to bridge this gap by quantifying and analyzing the drivers of Moodle’s technological acceptance among Ecuadorian academic staff. Considering the responses of 538 teachers and taking a modified UTAUT2 model as a theoretical basis, we found that Ecuadorian teachers have high levels of acceptance of Moodle, regardless of their age, gender, ethnicity, or discipline. However, this acceptance is significantly higher in teachers with high levels of education and with considerable previous experience with e-learning systems. The main determinants of this acceptance are attitude strength, effort expectancy, performance expectancy, and facilitating conditions. We found no moderating effects in relation to the age, gender, or previous experience of the participants (including second- and third-order interactions derived from these variables). We conclude that, albeit moderately (e.g., adjustedR2=0.588), the model tested confirms the predictive power of the part of UTAUT2 that was inherited from UTAUT.