This systematic review and meta-analysis aims to evaluate the effectiveness of internet-delivered cognitive behavioural therapy (ICBT) on anxiety and depression among persons with chronic health conditions. A systematic database search was conducted of MEDLINE, CINAHL, PsycInfo, EMBASE, and Cochrane for relevant studies published from 1990 to September 2018. A study was included if the following criteria were met: (1) randomized controlled trial involving an ICBT intervention; (2) participants experienced a chronic health condition; (3) participants ≥ 18 years of age; and (4) effects of ICBT on anxiety and/or depression were reported. The Cochrane Risk of Bias tool was used to assess the risk of bias on the included studies. Pooled analysis was conducted on the primary and condition specific secondary outcomes. Twenty-five studies met inclusion criteria and investigated the following chronic health conditions: tinnitus (n = 6), fibromyalgia (n = 3), pain (n = 7), rheumatoid arthritis (n = 3), cardiovascular disease (n = 2), diabetes (n = 1), cancer (n = 1), heterogeneous chronic disease population (n = 1), and spinal cord injury (n = 1). Pooled analysis demonstrated small effects of ICBT in improving anxiety and depression. Moderate effects of therapist-guided approach were seen for depression and anxiety outcomes; while, self-guided approaches resulted in small effects for depression and moderate effects in anxiety outcomes. ICBT shows promise as an alternative to traditional face-to-face interventions among persons with chronic health conditions. Future research on long-term effects of ICBT for individuals with chronic health conditions is needed.Trial Registration PROSPERO registration number: CRD42018087292.