Background <p>Classroom relationships are known to be one of the most important yet complex predictors of student well-being. However, this complexity is frequently not considered, and it remains unclear whether students with different well-being profiles and their transitions are impacted differently by teacher-student and student–student relationships.</p> Objective <p>This study aims to examine secondary school students’ well-being profiles, their transitions over time, and their connection to teacher-student and student–student relationships.</p> Methods <p>Participants included 757 Swiss secondary school students from grade 7 (47.8% female; <i>M</i>_age = 13.12, <i>SD</i>_age =.60) to grade 8 (44.6% female; <i>M</i>_age = 13.92, <i>SD</i>_age =.81). Latent profile analysis was conducted to classify students based on a multidimensional construct of student well-being, encompassing positive and negative emotions and cognitions toward school. To examine profile stability and transitions over time, latent transition analysis was used, and relationships with teacher-student closeness and conflict as well as student–student cohesion were analyzed.</p> Results <p>Four well-being profiles emerged: flourishing, perfectionist, worried, and ambivalent. Profiles varied in the composition of well-being dimensions, with school worries prevalent across all profiles. Students with high positive emotions transitioned to profiles with lower well-being, while those with high negative emotions remained in less favorable profiles. Teacher-student closeness and student–student cohesion supported favorable transitions, whereas teacher-student conflict hindered positive changes.</p> Conclusions <p>The identification of four distinct well-being profiles highlights individual differences in well-being and the interplay of positive and negative emotions. Teachers may play a pivotal role in preventing transitions to less favorable profiles, emphasizing the importance of fostering supportive classroom relationships.</p>