OBJECTIVE: Large health systems responding to the coronavirus disease 2019 (COVID-19) pandemic face a broad range of challenges; we describe 14 examples of innovative and effective informatics interventions. MATERIALS AND METHODS: A team of 30 physician and 17 nurse informaticists with an electronic health record (EHR) and associated informatics tools. RESULTS: To meet the demands posed by the influx of patients with COVID-19 into the health system, the team built solutions to accomplish the following goals: 1) train physicians and nurses quickly to manage a potential surge of hospital patients; 2) build and adjust interactive visual pathways to guide decisions; 3) scale up video visits and teach best-practice communication; 4) use tablets and remote monitors to improve in-hospital and posthospital patient connections; 5) allow hundreds of physicians to build rapid consensus; 6) improve the use of advance care planning; 7) keep clinicians aware of patients' changing COVID-19 status; 8) connect nurses and families in new ways; 9) semi-automate Crisis Standards of Care; and 10) predict future hospitalizations. DISCUSSION: During the onset of the COVID-19 pandemic, the UCHealth Joint Informatics Group applied a strategy of "practical informatics" to rapidly translate critical leadership decisions into understandable guidance and effective tools for patient care. CONCLUSION: Informatics-trained physicians and nurses drew upon their trusted relationships with multiple teams within the organization to create practical solutions for onboarding, clinical decision-making, telehealth, and predictive analytics.