Introduction: A systematic literature review and network meta-analysis (NMA) were conducted to compare the short-term efficacy of lebrikizumab to other biologic and Janus kinase (JAK) inhibitor monotherapies approved for moderate-to-severe atopic dermatitis in adults and adolescents. Methods: The NMA included randomized, double-blind, placebo-controlled monotherapy phase 2 and 3 trials of biologics (lebrikizumab 250 mg every 2 weeks [Q2W], dupilumab 300 mg Q2W, and tralokinumab 300 mg Q2W) and JAK inhibitors (abrocitinib 100/200 mg daily, baricitinib 2/4 mg daily, and upadacitinib 15/30 mg daily) at approved doses. Efficacy outcomes included the proportions of patients achieving Eczema Area and Severity Index (EASI) improvement, an Investigator Global Assessment of 0 or 1 (IGA 0/1), and a ≥ 4-point improvement in pruritus/itch numeric rating scale score at 12 weeks (abrocitinib) or 16 weeks (other treatments). Itch was also assessed at week 4. A Bayesian NMA employing baseline risk-adjusted random effects models was used to estimate treatment differences. Results: Twenty-two monotherapy studies involving 8531 patients were included in the NMA. By week 12/16, lebrikizumab had superior odds of achieving IGA 0/1 and itch improvement compared to baricitinib and tralokinumab; similar odds to dupilumab, abrocitinib, and upadacitinib 15 mg; and inferior odds to upadacitinib 30 mg. Additionally, lebrikizumab had a higher probability of improving EASI than baricitinib 2 mg; similar probability to baricitinib 4 mg, tralokinumab, dupilumab, abrocitinib, and upadacitinib 15 mg; and lower probability than upadacitinib 30 mg daily. At week 4, lebrikizumab had superior odds of improving itch compared to tralokinumab; similar odds to baricitinib, dupilumab, and abrocitinib 100 mg; and inferior odds to abrocitinib 200 mg and upadacitinib. Conclusion: Among biologics, lebrikizumab was comparable to dupilumab and superior to tralokinumab in improving response rates at week 16. Upadacitinib 30 mg was the only JAK inhibitor with superior response rates compared to lebrikizumab.