Collaborative argumentation (CA) is a prolific but challenging form of collaborative learning that requires group members to engage in a quantity of regulation to sustain the group's productive functioning. The purpose of this study was to investigate the differences between the high- and low-performing CA groups in terms of (a) challenges and triggered social regulation during CA, and (b) sequential patterns of social regulation used by those groups. From that, this research aimed to reveal what may promote or constrain CA from the perspective of social regulation. The target groups were selected from a larger sample of 14 groups based on the groups' argument diagram scores after they participated in a 90-min CA activity. Videos and interview data were collected and analyzed to reveal the encountered challenges and social regulation in the activity. Several findings were obtained. First, the low-performing groups encountered far more challenges and the biggest difference between the high- and low-performing groups was the socio-emotional challenges. Second, more challenges were regulated in low-performing groups, with more cognitive and socio-emotional challenges being regulated and less motivational challenges being handled. For cognitive challenges, the effective strategies to deal with the deadlock in reaching an agreement were identified among high-performing groups. For socio-emotional challenges, although more have been regulated in low-performing groups, the tense atmosphere made social regulation less successful. For motivational challenges, low-performing groups paid little attention to other members' participation. Third, the high- and low-performing groups demonstrated different sequential patterns, such as more transitions related to socio-emotional regulation and evaluation in high-performing groups. Pedagogical implications and the need to support students to cope with socio-emotional challenges are discussed in the last.