Lifespan is determined by complex and tangled mechanisms that are largely unknown. The early postnatal stage has been proposed to play a role in lifespan, but its contribution is still controversial. Here, we show that a short rapamycin treatment during early life can prolong lifespan in Mus musculus and Drosophila melanogaster. Notably, the same treatment at later time points has no effect on lifespan, suggesting that a specific time window is involved in lifespan regulation. We also find that sulfotransferases are upregulated during early rapamycin treatment both in newborn mice and in Drosophila larvae, and transient dST1 overexpression in Drosophila larvae extends lifespan. Our findings unveil a novel link between early‐life treatments and long‐term effects on lifespan. Synopsis This study reveals a link between early‐life treatments and long‐term effects on lifespan in Drosophila and mice. A short rapamycin treatment during early life prolongs lifespan in Mus musculus and Drosophila melanogaster while the same treatment at later time points has no effect on lifespan. Sulfotransferases are upregulated during early rapamycin treatment both in newborn mice and Drosophila larvae. Transient dST1 sulfotransferase overexpression in Drosophila larvae extends lifespan. This study reveals a link between early‐life treatments and long‐term effects on lifespan in Drosophila and mice.