Purpose: Youth and young adults are particularly vulnerable to the socio-economic impacts of Coronavirus Disease (COVID-19). The purpose of this study was to explore barriers to school and employment for youth with and without a disability during the pandemic. Methods: This qualitative comparison study involved in-depth interviews with 35 youth and young adults (18 with a disability; 17 without), aged 16–29 (mean age 23). An interpretive, thematic analysis of the transcripts was conducted. Results: Our findings revealed several similarities and some differences between youth and young adults with and without disabilities regarding barriers to school and employment during the COVID-19 pandemic. Key themes related to these barriers involved: (1) difficult transition to online school and working from home (i.e., the expense of setting up a home office, technical challenges, impact on mental health), (2) uncertainty about employment (i.e., under-employment, difficult working conditions, difficulty finding work, disability-related challenges) and (3) missed career development opportunities (i.e., canceled or reduced internships or placements, lack of volunteer opportunities, uncertainties about career pathway, the longer-term impact of the pandemic). Conclusion: Our findings highlight that youth and young adults with disabilities may need further support in engaging in meaningful and accessible vocational activities that align with their career pathway.