This study investigates the contextual and relational characteristics that underlie people’s information and communication technology (ICT) use and the implications for their well-being. We contextualize this investigation according to migrants, because they are faced with disruptions to their personal networks in the migration process that may attenuate the availability of social support and negatively affect their mental health. Migrants tend to be proficient in using mobile ICT to connect with different social ties to fulfill their needs, which potentially makes a difference to their psychological well-being. Through a survey of 504 internal migrant workers in China, we examined the social network factors that underlie multiple mobile ICT use and the attendant influences on social support and psychological well-being. Redressing the overemphasis on the importance of strong ties in extant literature, this study highlights the salience of mobile media multiplexity (i.e., the use of multiple mobile communication channels for social interactions) in weak tie communication and the greater contribution of weak ties toward social support and psychological well-being than strong ties. Our findings suggest that mobile-mediated communicative relationships with newer and more distanced social connections outside their immediate circles enhance the well-being of migrants. We contend that media multiplexity vis-à-vis weak ties underscores the reconfiguration of migrants’ communicative relationships following the separation from original ties and facilitates rewarding interactions with new ties.