Straus first achieved prominence as a merchant, becoming in 1896 a co-owner with his brother Isidor Straus of R.H. Macy and Company. His philanthropic work began in the economic depression of 1892 when he distributed food and coal in New York City and supplied pasteurized milk to young children in 36 American cities, thus lowering the infant mortality rate. By 1920 he had established 297 milk-distribution depots in the United States and abroad.

In 1909 Straus built the first tuberculosis preventorium for children in Lakewood, N.J., and he provided food for the poor during the harsh winter of 1914–15 in New York City. The last 20 years of his life, largely devoted to public-health work in Palestine, resulted in the building of two major health centres and many child-welfare stations.