Answer by Raakhee V. Menon:
According to Hindu shastras, the most powerful weapon is the Brahmandastra.
Wikipedia has a wonderful write-up about this astra
In the epic Mahabharata, it is said that the weapon manifest with the all five heads of Lord Brahma as its tip. Lord Brahma lost his fifth head when he fought with Lord Shiva. This weapon is said to possess the power to destroy the Universe and its 14 realms, according to Hindu cosmology. In Mahabharata era the characters Parasurama, Bhishma, Drona, Karna possessed the knowledge to invoke this weapon.
As recorded in Hindu puranas, when this weapon is invoked, it will cause ” the oceans to boil due to its heat and earth and mountains will float on the air and everything will burn without even leaving ashes”. When this weapon is used for defensive purpose or to counter the Brahmastra and Brahmashirsha astra, it will swallow both astras and neutralize it. When this astra is used for offensive purposes, nothing can stop or even escape from it. In some texts it is called Brahma-dhanda astra. The weapon was created by Saptarishi’s to counter any weapon ever created, even that of Trimurti’s. The rishi of this weapon is Para Brahman. It is said to be the most difficult astra to obtain. Capable of destroying entire multiverse in a blink of an eye. Vishvamitra used all kinds of divine weapons against sage Vashistha, but the Brahma-dhanda astra of sage Vashistha neutralized and swallowed all astra (weapon) of Vishwamitra proving that the Brahma-dhanda astra is the most powerful of all astra’s. On 17th day of Kurukshetra war, Pandava army was saved from the hands of Karna who tried to invoke the astra owing due to curse from Parashurama.
The Brahmanda Astra is a defensive weapon that is capable of destroying any celestial weapon. Its power is said to be so immense and so intense that it could destroy creation itself.
In the Mahabharata, it is mentioned that only Lord Parashurama, Bhishma, Dronacharya and Karna had the knowledge to invoke this weapon. If Karna had not been cursed by Parashurama, he would have used it against the Pandava army and finished the war in a matter of seconds.