New multicomponent domino reactions (MDRs) have been established for the synthesis of spiro(pyrazolo[1,3]dioxanopyridine)-4,6-diones, spiro(isoxazolo[1,3]dioxanopyridine)-4,6-diones and pyrazolo[3,4-b]pyridines. The MDRs were conducted by reacting readily available and inexpensive starting materials in aqueous solution under microwave irradiation. A total of 26 examples were examined, and showed a broad substrate scope and high overall yields (76–93%). A new mechanism has been proposed to explain the reaction process and the resulting chemo-, regio- and stereoselectivity. The present green synthesis shows attractive characteristics such as the use of water as the reaction medium, one-pot conditions, short reaction periods (9–13 min), easy work-up/purification and reduced waste production without the use of any acids or metal promoters.