Background: The Matthey Generic Mood Questionnaire (MGMQ) provides a rapid screen of clinically significant emotional difficulties in adults. This study aimed to investigate associations between the MGMQ and Depression Anxiety Stress Scales short-form (DASS-21) and how well the MGMQ detects women scoring high on the DASS-21 in pregnancy and 1 and 2 years postpartum. Methods: Pregnant Australian, English-speaking women were recruited from 10 maternity hospitals across two states (for the “right@home” trial, N=729). Prioritized for their experience of social adversity (2 or more of 10 risk factors), they completed the 2-item MGMQ and 21-item DASS-21 in pregnancy and at 1 and 2 years postpartum. DASS-21 Total and subscale scores were classified “high” based on (a) normed percentiles for top 15% and (b) clinical cut-points. Results: The MGMQ and DASS-21 were completed within 7 days of each other by 296 (41%) women in pregnancy, 625 (86%) at 1 year and 573 (79%) at 2 years. Associations between the measures were weak-to-moderate in pregnancy and moderate-to-strong in the postpartum years. Most women scoring “high” on the DASS-21 could be identified with various thresholds of the MGMQ. Limitations: Pregnant women with 0 or 1 risk factor were excluded; the DASS-21 is not a perinatal specific measure nor a gold standard diagnostic tool. Conclusions: The MGMQ and DASS-21 appeared to assess overlapping but distinct constructs of mental health. These findings can help clinicians and researchers decide whether to use the MGMQ, and which balance of sensitivity, specificity and correct classification will suit their needs.