ABSTRACT: (1) Background: Psychological problems of adolescents have become a global health and safety concern. Empirical evidence has shown that adolescents experience diverse mental health conditions (e.g., anxiety, depression, and emotional disorders). However, research on anxiety-induced sleep disturbance among in-school adolescents has received less attention, particularly in low- and middle-income countries. This study's central focus was to examine factors associated with t anxiety-induced sleep disturbance among in-school adolescents in Ghana. (2) Methods: Analysis was performed using the 2012 Global School-based Health Survey (GSHS). A sample of 1342 in-school adolescents was included in the analysis. The outcome variable was anxiety-induced sleep disturbance reported during the past 12 months. Frequencies, percentages, chi-square, and multivariable logistic regression analyses were conducted. Results from the multivariable logistic regression analysis were presented as crude and adjusted odds ratios at 95% confidence intervals (CIs) and with a statistical significance declared at p < 0.05. (3) Results: Adolescents who went hungry were more likely to report anxiety-induced sleep disturbance compared to their counterparts who did not report hunger (aOR = 1.68, CI = 1.10, 2.57). The odds of anxiety-induced sleep disturbance were higher among adolescents who felt lonely compared to those that never felt lonely (aOR = 2.82, CI = 1.98, 4.01). Adolescents who had sustained injury were more likely to have anxiety-induced sleep disturbance (aOR = 1.49, CI = 1.03, 2.14) compared to those who had no injury. Compared to adolescents who never had suicidal ideations, those who reported experiencing suicidal ideations had higher odds of anxiety-induced sleep disturbance (aOR = 1.68, CI = 1.05, 2.71). (4) Conclusions: Anxiety-induced sleep disturbance among in-school adolescents were significantly influenced by the psychosocial determinants such as hunger, loneliness, injury, and suicidal ideation in this study. The findings can help design appropriate interventions through effective strategies (e.g., early school-based screening, cognitive-behavioral therapy, face-face counseling services) to reduce psychosocial problems among in-school adolescents in Ghana.