Objective To systemically assess efficacy and safety of upadacitinib (UPA), a selective inhibitor of Janus kinase 1 (JAK1) in treatment of ankylosing spondylitis (AS). Methods Available databases were used to retrieve literatures of randomized controlled trials (RCTs) of UPA for AS treatment until February 2024. After that, the data were extracted and the Revman 5.4 software was used to conduct a meta-analysis. Results A total of 6 articles and 1653 patients (920 in a UPA group (15 mg, q.d) and 733 in a placebo group) were selected in this study. Respectively, UPA treatment significantly increased numbers of the AS patients having 40%, 20%, or partial remission (PR) improvement in assessment of spondylo arthritis international society (ASAS) (ASAS 40: 95%CI: 2.41-4.3, p < 0.00001; ASAS 20: 95%CI: 2.12-3.62, p < 0.00001; ASAS PR: 95%CI: 2.81-7.48, p < 0.00001), Bath ankylosing spondylitis disease activity index (BASDAI50) (95%CI: 2.28 similar to 4.10, p < 0.00001), quality of life (95%CI: 2.06 similar to 3.17, p < 0.00001), AS disease activity score low disease activity (ASDAS LDA) (95%CI: 3.07 similar to 9.96, p < 0.00001), ASDAS inactive disease (ID) (95%CI: 2.03 similar to 17.22, p = 0.001), short-form 36 physical component summary (SF-36PCS) (95%CI: 1.53 similar to 2.81, p < 0.00001), and markedly reduced ASDAS C-reactive protein (CRP) (95%CI: -1.22 similar to -0.42, p < 0.0001), total back pain score (95%CI: -2.01 similar to -0.51, p = 0.001), nighttime back pain score (95%CI: -1.96 similar to -0.54, p = 0.0006), spondylo arthritis research consortium of Canada magnetic resonance imaging (SPARCC MRI) spine score (95%CI: -7.78--3.50, p < 0.00001) and SPARCC MRI sacroiliac joint score (95%CI: -5.99 - -3.09, p < 0.00001), Bath ankylosing spondylitis function index (BASFI) score (95%CI: -1.45 similar to -0.81, p < 0.00001), Maastricht ankylosing spondylitis enthesitis score (MASES) (95%CI: -2.34 similar to-0.35, p = 0.008). Except for neutropenia (95%CI: 1.25 similar to 15.60, p = 0.02), no other adverse effects (AEs) were significantly different between the UPA treatment and placebo. Conclusions Through a literature analysis, it reveals that UPA offers significant therapeutic benefits to AS patients with a relatively high safety profile.