This paper combines the knowledge structure of English and American literature and learners’ personalized knowledge characteristics to design and propose personalized teaching based on a genetic algorithm. Genetic algorithms are used to extract learner characteristics, and content-based recommendation algorithms are applied to match ability characteristics, goal characteristics and learning object characteristics to achieve personalized course teaching. The crossover probability, variation probability, selection operator and crossover operator of the genetic algorithm are determined, and simulation experiments are designed to analyze the optimization effect of its parameters. Setting three levels of colleges and universities, with the connotation of the objectives and level positioning of English and American literature teaching, i.e., reading experience, reading knowledge, reading method, and the cultivation of cultural connotation and humanistic sentiment as factors, a one-way ANOVA was carried out to examine whether the teaching objectives of different levels of colleges and universities differed significantly in personalized teaching. In terms of the highest level of the teaching objectives of English and American literature, i.e., the cultivation of humanistic sentiment, F=6.607, Sig=0.002, 985 colleges>211 colleges and universities, and general undergraduate schools>211 colleges and universities.