Background No published research in Ethiopia has examined the prevalence of suicidal ideation and suicide attempts and associated factors among patients with substance use disorder. Aims The main aim of this study was to assess the prevalence of suicidal ideation, suicide attempt and associated factors among patients with substance use disorders. Method An institution-based cross-sectional study was conducted from 5 May to 13 June 2019 in Addis Ababa. A total of 408 patients were identified using a systematic sampling technique. Data were collected through interviews using the suicidality module of the Composite International Diagnostic Interview. Data were entered into EpiData and analysed using SPSS. Logistic regression analyses were employed. Variables with P < 0.05 were considered to be statistically significant with 95% confidence intervals. Results Prevalence rates of suicidal ideation and attempt were found to be 39.5% and 18.6%, respectively. Family history of mental illness (adjusted odds ratio (AOR) = 3.60, 95% CI: 2.17, 5.97), comorbid mental illness (AOR = 3.61, 95% CI: 2.11, 6.16), perceived stigma related to substance misuse (AOR = 4.00, 95% CI: 2.26, 7.07) and alcohol use (AOR = 7.49, 95% CI: 1.99, 28.19) were associated with suicidal ideation. Being female (AOR = 2.46, 95% CI: 1.08, 5.70), family history of suicide (AOR = 3.08, 95% CI: 1.68, 5.64), comorbid mental illness (AOR = 4.09, 95% CI: 2.23, 7.49) and khat use (AOR = 3.73, 95% CI: 1.24, 11.17) were associated with suicide attempt. Conclusions The prevalence of suicidal ideation and attempt were both found to be high. In particular, patients who had a comorbid mental illness were at high risk of both suicidal ideation and attempt. Therefore, special attention should be given to those with a family history of suicide or comorbid mental illness.