Aim: To investigate the association between clusters of conditions and psychological well-being across age groups. Method: This cross-sectional study used data collected in the Danish population-based Lolland-Falster Health Study. We included adults over the age of 18 years. Self-reported chronic conditions were divided into 10 groups of conditions. The primary outcome was psychological well-being (the WHO-5 Well-Being Index). Factor analysis constructed the clusters of conditions, and regression analysis investigated the association between clusters and psychological well-being. Results: Of 10,781 participants, 31.4% were between 18 and 49 years, 35.7% were between 50 and 64 years and 32.9% were above ≥65 years. 35.2% had conditions represented in 1 and 32.9% in at least 2 of 10 condition groups. Across age groups, living with one or more chronic conditions was associated with poorer psychological well-being. Two chronic condition patterns were identified; one comprised cardiovascular, endocrine, kidney, musculoskeletal and cancer conditions, the second mental, lung, neurological, gastrointestinal and sensory conditions. Both patterns were associated with poorer psychological well-being (Pattern 1: −4.5 (95% CI: −5.3 to −3.7), Pattern 2: −9.1 (95% CI −13.8 to −8.2). For pattern 2, participants ≥65 years had poorer psychological well-being compared to younger (−12.6 (95% CI −14.2 to −11.0) vs −6.6 (95% CI: −7.8 to −5.4) for 18–49 years and −8.7 (95% CI: −10.1 to −7.3) for 50–64 years, interaction: p ≤ 0.001) Conclusion: Living with one or more chronic conditions is associated with poorer psychological well-being. Findings point toward a greater focus on supporting psychological well-being in older adults with both mental and somatic conditions.