The recent decades have ushered in considerable advancements in the diagnosis and treatment of systemic light chain (AL) amyloidosis. As disease outcomes improve, AL amyloidosis-unrelated factors may impact mortality. In this study, we evaluated survival trends and primary causes of death among 2337 individuals with AL amyloidosis referred to the Boston University Amyloidosis Center. Outcomes were analyzed according to date of diagnosis: 1980-1989 (era 1), 1990-1999 (era 2), 2000-2009 (era 3), and 2010-2019 (era 4). Overall survival increased steadily with median values of 1.4, 2.6, 3.3, and 4.6 years for eras 1-4, respectively (P < 0.001). Six-month mortality decreased over time from 23% to 13%. Wide gaps in survival persisted amid patient subgroups; those with age at diagnosis ≥70 years had marginal improvements over time. Most deaths were attributable to disease-related factors, with cardiac failure (32%) and sudden unexpected death (23%) being the leading causes. AL amyloidosis-unrelated mortality increased across eras (from 3% to 16% of deaths) and with longer-term survival (29% of deaths occurring >10 years after diagnosis). Under changing standards of care, survival improved and early mortality declined over the last 40 years. These findings support a more optimistic outlook for patients with AL amyloidosis.