Sexual minority men and transgender women are disproportionately affected by HIV in Guatemala. Innovative prevention strategies are urgently needed to address these disparities. While social network approaches are frequently used to reach sexual minorities, little is known about the unique network characteristics among sub-groups. We conducted in-depth qualitative interviews with 13 gay-identifying men, eight non-gay-identifying men who have sex with men (MSM) and eight transgender women in Guatemala City. Using narrative and thematic coding procedures, we identified distinct patterns in the size, composition, and overlap between social and sexual networks across groups. Gay-identifying men had the largest, most supportive social networks, predominantly comprising family. For both non-gay-identifying MSM and transgender women, friends and sex clients provided more support. Transgender women reported the smallest social networks, least social support, and the most discrimination. HIV prevention efforts should be tailored to the specific sexual minority population and engage with strong ties.