Year 221 BC was a year of the pre-Julian Roman calendar. At the time it was known as the Year of the Consulship of Asina and Rufus/Lepidus (or, less frequently, year 533 Ab urbe condita). The denomination 221 BC for this year has been used since the early medieval period, when the Anno Dominicalendar era became the prevalent method in Europe for naming years.
The Carthaginian general Hasdrubal is murdered by a Celtic assassin while campaigning to increase the Carthaginian hold on Spain. Following the assassination of Hasdrubal, Hannibal, the son of the Carthaginian general, Hamilcar Barca, is proclaimed commander-in-chief by the army and his appointment is confirmed by the Carthaginian government.
Hannibal immediately moves to consolidate Carthage's control of Spain. He marries a Spanish princess, Imilce, then begins to conquer various Spanish tribes. He fights against the Olcades and captures their capital, Althaea; quells the Vaccaei in the northwest; and, making the seaport of Cartagena (Carthago Nova, the capital of Carthaginian Spain) his base, wins a resounding victory over the Carpetani in the region of the Tagus River.
The satrap of Media, Molon, and his brother, Alexander, revolt against Antiochus III, primarily due to their hatred towards Hermeias, Antiochus' chief minister. Molon is able to become master of the Seleucid domains to the east of the Tigris. He is stopped by Antioochus III's forces in his attempts to pass that river. Xenoetas, one of Antiochus' generals, is sent against Molon with a large force, but is surprised by Molon's forces and his whole army is cut to pieces and Xenoetas is killed. The rebel satrap now crosses the Tigris, and makes himself master of the city of Seleucia on the Tigris, together with the whole of Babylonia and Mesopotamia.
The state of Qi – by now the only other independent state in China – surrenders to the state of Qin without a fight. Ying Zheng, the king of Qin unifies China and proclaims himself the First Emperor, as he is the first Chinese sovereign able to rule the whole country, thus ending the Warring States period. He is known by historians as Qin Shi Huang.