There are two problems in the traditional teaching of microbiology. First, the teaching cannot meet the diverse and individualized needs of students. Second, the students lack motivation and interest in learning because of their vague ambition and the abstruse nature of microbiology. To solve these problems, the microbiology teaching team adopted student-centered and output-oriented strategy to innovate the teaching method. Specifically, the team helped students establish faith, serve our country, and revitalize the rural area in a way that enabled then to find their sparks and plan of life. The teaching design was also innovated, which consisted of self-study before class, discussion in class, and practice after class, achieving seamless docking between online and offline teaching. Moreover, innovative measures were implemented according to innovation requirements, high-level standards, and challenge degrees, including perception after each class, experience and extended learning. These measures developed sufficient teacher-student and student-student interactions. Meanwhile, curriculum ideological and political education was designed to run through the teaching process. Finally, a multiple evaluation system was formed for the innovative teaching. Students were satisfied with this reform, demonstrating significantly improved participation rate of entrepreneurship and innovation projects, admission rate for postgraduate entrance, academic performance, and discipline competition achievement. The results can provide references for innovative reform of microbiology teaching.