Tokugawa Iemitsu was born around 1604 (his exact birthdate is unknown). He was the eldest son of Tokugawa Hidetada and grandson of the last great unifier of Japan, the first Tokugawa Shogun Tokugawa Ieyasu. He was the first member of the Tokugawa family born after Tokugawa Ieyasu became shogun.

Not much is known of Iemitsu's early life; his childhood name was Takechiyo (竹千代). He had two sisters, Senhime and Masako, and a brother, who would become a rival, Tadanaga. Tadanaga was his parents' favorite. However, Ieyasu made it clear that Iemitsu would be next in line as shogun after Hidetada. An obsolete spelling of his given name is Iyemitsu.

Iemitsu came of age in 1617 and dropped his childhood name in favor of Tokugawa Iemitsu. He also was installed officially as the heir to the Tokugawa shogunate. The only person to contest this position was his younger brother Tokugawa Tadanaga. A fierce rivalry began to develop between the brothers.

From an early age Iemitsu practiced the shudo tradition. However, in 1620, he had a falling out with his lover, Sakabe Gozaemon, a childhood friend and retainer, aged twenty one, and murdered him as they shared a bathtub.

In 1623, when Iemitsu was nineteen, Hidetada abdicated the post of shogun in his favor. Hidetada continued to rule as Ōgosho (retired Shogun), but Iemitsu nevertheless assumed a role as formal head of the bakufu bureaucracy.

In 1626, Shogun Iemitsu and retired Shogun Hidetada visited Emperor Go-Mizunoo, Empress Masako (Hidetada's daughter and Iemitsu's sister), and Imperial Princess Meisho in Kyoto. Shogun Iemitsu made lavish grants of gold and money to the court nobles and the court itself. Yet relations with Go-Mizunoo deteriorated after the Purple Clothes Incident (紫衣事件 shi-e jiken^?), during which the Emperor was accused of having bestowed honorific purple garments to more than ten priests despite an edict which banned them for two years (probably in order to break the bond between the Emperor and religious circles). The shogunate intervened, making the bestowing of the garments invalid. When the wet nurse of Iemitsu and Masako broke a taboo by visiting the imperial court as a commoner, Go-Mizunoo abdicated, embarrassed, and Meisho became empress. The shogun was now the uncle of the sitting monarch.

In Kan'ei 9, on the 24th day of the 2nd month (1632), Ōgosho Hidetada died, and Iemitsu could assume real power. Worried that his brother Tokugawa Tadanaga might assassinate him, however, he ruled carefully until that brother's death by Seppuku in 1633.

Hidetada left his advisors, all veteran daimyo, to act as regents for Iemitsu. In 1633, after his brother's death, he dismissed these men. In place of his father's advisors, Iemitsu appointed his childhood friends. With their help Iemitsu created a strong, centralized administration. This made him unpopular with many daimyo, but Iemitsu simply removed his opponents.

He is credited with establishing the Sankin kōtai system which forced tozama daimyo to reside in Edo in alternating sequence — one year in Edo and one year in the home region.

In 1637 an armed revolt arose against Iemitsu's anti - Christian policies in Shimabara. This period domestic unrest is known as the Shimabara Rebellion. Thousands were killed in the shogunate's suppression of the revolt and countless more were executed afterwards.

In 1639 Iemitsu officially closed off Japan from the rest of the world. This restrictive edict limiting trade to the Chinese and Dutch merchants ensconced on the island of Deshima in Nagasaki and the proxy trade with China carried out by the Ryukyu Kingdom under the control of the Shimazu clan.

In 1643 Empress Meisho abdicated the throne. She was succeeded by her younger half - brother (Go-Mizunoo's son by a consort) Emperor Go-Komyo, who disliked the shogunate for its violent and barbaric ways. He repeatedly made insulting comments about Iemitsu and his eldest son and heir, Tokugawa Ietsuna.

In 1651 Shogun Iemitsu died at the age of 47, being the first Tokugawa shogun whose reign ended with death and not abdication. He was accorded a posthumous name of Taiyūin, also known as Daiyūin. He was succeeded by his eldest son and heir, Tokugawa Ietsuna.

During the 16th century, Japan was among the countries in Asia that appealed most to European traders and missionaries. In 1543, the first Europeans, from Portugal, arrived at the island of Tanegashima, thus inaugurating the so-called Nanban trade (南蛮貿易 Nanban bōeki) period. From 1545 onwards, Japan saw the arrival of numerous European ships, first from Portugal, and later from Spain, the Netherlands and England. Starting in 1549, with the arrival of Francis Xavier at Kagoshima, a large campaign of evangelization, led by the Society of Jesus, was shaking Japan's social structures. What is more, on the island of Kyūshū, in order to preserve the European trade in their lands, some feudal rulers known as daimyo agreed to be converted to Christianity. By the beginning of the 17th century half - a - million Japanese people had converted to Christianity.

However, during this period of Europeanization, adverse feelings towards the foreigners started spreading across Japan. Moreover, after Spain’s conquest of the Philippines, the then ruler Hideyoshi lost faith in Europeans’ good intentions and started doubting the loyalty of the newly converted daimyo. The first step to the expulsion of the foreign traders and missionaries was made by him when he ordered the crucifixion of the main Catholic proselytizers and converts. But it was not until the reign of Tokugawa Iemitsu that more drastic measures were taken.

Europeans’ century long presence in Japan ended in the 1630s when Iemitsu ordered the expulsion of every European from the country. Moreover, he gave permission to only one Dutch ship to trade with Japan per year. His orders were reinforced after the execution of two Portuguese men who came to plead for the re-establishment of Japan’s earlier foreign trade policy. In the 1630s, Iemitsu issued several isolationist edicts which prohibited people and goods, with a few exceptions, to enter or leave the country.

The most famous of those edicts was the Closed Country Edict of 1635. It contained the main restrictions introduced by Iemitsu. With it, he forbade every Japanese ship and person to travel to another country. The punishment for violation was death. The same thing applied to those who came from overseas. They too were risking death if they decided to enter Japan. The edict offered lavish gifts and awards for anyone who could provide information about priests and their followers who secretly practiced and spread their religion across the country. Furthermore, every newly arrived ship was required to be thoroughly examined for Catholic priests and followers. The document pays extremely close attention to every detail regarding incoming foreign ships. For example, the merchants coming from abroad had to submit a list of the goods they were bringing with them before being granted permission to trade them. Also, they were not allowed to sell their merchandise to just one of the trading cities of Japan. In this way, better distribution of goods was ensured. Additional provisions specified details of trade. For example, the “date of departure homeward for foreign ships shall not be later than the twentieth day of the ninth month.” In addition to this, Iemitsu forbade the changing of the originally set price for raw silk and thus made sure that competition between trading cities was brought to a minimum.

The measures Iemitsu enacted were so powerful that it was not until the reign of Tokugawa Ienobu, more than half a century later, that the seclusion of Japan began to fade.

Iemitsu's rivalry with his brother Tokugawa Tadanaga over the Shogunate form a part of the television series The Yagyu Conspiracy and is the basis for the film Shogun's Samurai (at the end of the film, Shogun Iemitsu is killed and decapitated by Yagyu Jubei in an act of revenge for his father Yagyū Munenori's betrayal).