The World Health Organization (WHO) recently put forth a Global Strategy on Digital Health 2020–2025 with several countries having already achieved key milestones. We aimed to understand whether and how digital health technologies (DHTs) are absorbed in Africa, tracking Ethiopia as a key node. We conducted a systematic review, searching PubMed-MEDLINE, Embase, ScienceDirect, African Journals Online, Cochrane Central Registry of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to 02 February 2021 for studies of any design that investigated the potential of DHTs in clinical or public health practices in Ethiopia. This review was registered with PROSPERO (CRD42021240645) and it was designed to inform our ongoing DHT-enabled randomized controlled trial (RCT) (ClinicalTrials.gov ID: NCT04216420). We found 27,493 potentially relevant citations, among which 52 studies met the inclusion criteria, comprising a total of 596,128 patients, healthy individuals, and healthcare professionals. The studies involved six DHTs: mHealth (29 studies, 574,649 participants); electronic health records (13 studies, 4534 participants); telemedicine (4 studies, 465 participants); cloud-based application (2 studies, 2382 participants); information communication technology (3 studies, 681 participants), and artificial intelligence (1 study, 13,417 participants). The studies targeted six health conditions: maternal and child health (15), infectious diseases (14), non-communicable diseases (3), dermatitis (1), surgery (4), and general health conditions (15). The outcomes of interest were feasibility, usability, willingness or readiness, effectiveness, quality improvement, and knowledge or attitude toward DHTs. Five studies involved RCTs. The analysis showed that although DHTs are a relatively recent phenomenon in Ethiopia, their potential harnessing clinical and public health practices are highly visible. Their adoption and implementation in full capacity require more training, access to better devices such as smartphones, and infrastructure. DHTs hold much promise tackling major clinical and public health backlogs and strengthening the healthcare ecosystem in Ethiopia. More RCTs are needed on emerging DHTs including artificial intelligence, big data, cloud, cybersecurity, telemedicine, and wearable devices to provide robust evidence of their potential use in such settings and to materialize the WHO’s Global Strategy on Digital Health.