Risk factors associated with developing opioid use disorders (OUD) are documented, but less is known about different pathways to initiation of opioids or opioid dependence, or how such pathways affect treatment engagement. We recruited 283 adults with electronic medical record (EMR) evidence of opioid dependence diagnoses. Open-ended and structured interview items focused on prior opioid treatment experiences, barriers to and knowledge of treatment options. Interviews were audio-recorded, transcribed, and coded. In exploratory analyses, we used a modified grounded theory approach to organize emergent, patient-reported themes describing participants’ perceived pathways to opioid dependence. 121 participants described one or more pathways to OUD. Qualitative analyses revealed five pathway themes. Three pathways were related to pain control: inadequately controlled chronic pain, exposure to opioids during acute pain episodes, and chronic pain among individuals with prior substance use disorders. A fourth pathway included individuals for whom opioids provided relief from emotional distress; the fifth related to recreational or non-medically supervised opioid use. We identified pain-related barriers to reducing/stopping opioids and treatment engagement barriers among individuals who perceived themselves solely as pain patients. Patients’ perceptions of inadequately controlled pain, patients’ previous substance use disorders, and the relief from emotional distress that some patients feel while using opioids are relevant when making clinical decisions about whether to initiate or sustain opioid therapy, and for how to monitor certain individuals. Among individuals with pain and OUD, treatment barriers include fear of uncontrolled pain, and stigmatization of being treated alongside people with non-medical opioid use.