This study explores toxic stress and youth disconnection from work and school using data from the Detroit Jobs for Michigan's Graduates (JMG) program. A secondary cross‐sectional analysis was conducted using a program census of 1934 youth participating in JMG between 2014 and 2019. Youth with criminal justice contact, parenting responsibilities, and toxic stress barriers showed the greatest disparity in graduating or become employed following participation in the JMG program. Youth without toxic stress‐aligned barriers were 1.87 times the odds more likely of successful program outcomes when controlling for program enrollment year, program type, Detroit residency, gender, and age. Toxic stress is associated with disconnection from education and employment before and after participation in the JMG program. This indicates that expanding trauma‐informed systems and community approaches in youth‐serving programs can play a role in mitigating the impact of toxic stress exposure on connection to opportunity for Detroit youth.