This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF‐38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH‐23390 abolished the effects of SKF‐38393. In OS732 cells, overexpression of DR1 increased the rate of apoptosis, caspase‐9 and ‐3 expression, and the release of cytochrome c (Cyt c), reduced Bcl‐2 expression, inhibited extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation, and induced phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK) and c‐Jun N‐terminal kinase (JNK). These results suggest that activation of DR1 induces osteosarcoma cell apoptosis via changes to the MAPK pathway.