Deng Sui was born in 81. Her father Deng Xun (鄧訓) was a son of Emperor Guangwu's prime minister Deng Yu. Her mother, Lady Yin, was a daughter of a cousin of Emperor Guangwu's wife Empress Yin Lihua. She had a noted interest in studying, being able to read historical texts at age six and being able to recite the shujing and lunyu when she was twelve.
She was selected to be in the palace in 95. She became a consort to Emperor He in 96, when she was 15, and he was 17.
When Deng Sui became an imperial consort, Emperor He had already created Empress Yin empress. Empress Yin was described as beautiful but short and clumsy, and she was also known for jealousy. Consort Deng tried to foster a proper relationship with her by being humble, and was described as constantly trying to cover Empress Yin's mistakes. This, however, only drew Empress Yin's jealousy, as Emperor He became impressed with her and considered her one of his favorites. Empress Yin was also not pleased that Consort Deng, concerned that Emperor He was constantly losing sons in childhood, often recommended other consorts for him to have sexual relations with. Once, when Emperor He was ill, Empress Yin made the remark that if she became empress dowager, the Dengs would be slaughtered—and upon hearing that remark, Consort Deng considered committing suicide, and one of her ladies in waiting saved her by falsely telling her that the emperor had recovered. However, the emperor did soon recover, so Consort Deng and her family escaped a terrible fate.
In 102, Empress Yin and her grandmother, Deng Zhu (鄧朱), were accused of using witchcraft to curse imperial consorts (probably including Consort Deng). She was deposed and died of sorrow, probably in 102 as well. Emperor He created Consort Deng empress to replace her.
As empress, Empress Deng was described as diligent and humble, and she resisted offers by Emperor He to promote her relatives. She was taught by Ban Zhao, whom she made a Lady-in-Waiting.
She also prohibited the commanderies and principalities from offering her tributes—which had been customary for empresses to receive.
In 106, Emperor He died, creating a succession crisis. Empress Deng and all of the imperial consorts had been sonless for a long time. (Emperor He was described to have had a number of sons who died in young age; it is unclear whether Empresses Yin or Deng ever gave birth, but it appears that they did not.) Late in Emperor He's reign, he had two sons—whose mothers were not mentioned in history—Liu Sheng and Liu Long. Under the superstition of the time, it was thought that they might survive better if they grew up outside the palace in light of their other brothers' early deaths, so both were given to foster parents.
At the time Emperor He died, Liu Sheng, the older son, was still young (but actual age is not recorded in history) and believed to be constantly ill. The younger, Liu Long, was only 100 days old. Both were welcomed back to the palace, and Empress Deng created Liu Long crown prince, believing that he would be healthier, and then that night he was proclaimed emperor, as Emperor Shang. Power was in Empress Dowager Deng's hands, as regent for the infant emperor, and her brother Deng Zhi (鄧騭) quickly became the most powerful official at court. She also sought the advice of Ban Zhao, until her death in 116. She issued a general pardon, which benefitted the people who had rights stripped from them for associating with the family of Empress Dou, whose family had been powerful during the early reign of Emperor He but had been toppled in a coup d'état.
Late in 106, the young emperor died, creating yet another succession crisis. By this time, the officials had realized that Prince Sheng (then Prince of Pingyuan) was not as ill as initially thought, and they generally wanted him to be emperor. However, Empress Dowager Deng, concerned that Prince Sheng would bear a grudge for not having been made emperor first, had other ideas. She insisted on making Emperor Shang's cousin Prince Hu, who was seen by some as the rightful heir, emperor instead. He took the throne as Emperor An, at age 12.
When Emperor An ascended the throne, his father Liu Qing was still alive, as was his wife Consort Geng—who had remained in the capital Luoyang with him until his ascension. (Emperor An's mother Consort Zuo Xiao'e (左小娥), Liu Qing's concubine, had died sometime earlier.) However, Deng Sui was able to ensure exclusive control over the young emperor still, as empress dowager, by sending Consort Geng to join her husband Liu Qing in his Principality of Qinghe.
Deng Sui showed herself to be an able regent who did not tolerate corruption, even by her own family members. She also carried out criminal law reforms. For example, in 107, she issued an edict that extended the period for death penalty appeals. She cut a lot of the expenses at the royal court, like the making of expensive handicrafts such as jade and ivory carvings and sent home palace attendants with superfluous functions. She also demanded less tribute from the provinces.
In 107, however, there would be major problems on the borders. First, kingdoms of the Western Regions (or Xiyu, modern Xinjiang and Central Asia), which had submitted to Han suzerainty during the times of the great general Ban Chao, had been resisting Ban's successors for some time due to their harsh regulations, and in 107, Empress Dowager Deng finally decreed that Xiyu be abandoned. That same year, Qiang tribes, who had been oppressed by Han officials for more than a decade and fearful that they would be ordered to quell Xiyu rebellions, rebelled themselves. This was a major rebellion, affecting a wide region over modern Shaanxi, Gansu, and northern Sichuan, and Qiang forces even made incursions into modern Shanxi and threatened the capital at one point. The situation became so severe that Deng Zhi considered abandoning Liang Province (涼州, roughly modern Gansu), a proposal that Empress Dowager Deng wisely rejected. The rebellion would not be put down until 118, by which point the western empire was in shambles.
Also, in 107 to 109, there were many natural disasters—floods, droughts, and hail, in different parts of the empire. Empress Dowager Deng was largely effective in organizing disaster relief efforts.
In 109, South Xiongnu, which had been a loyal vassal up to this point, rebelled as well, believing that Han had been so weakened by Qiang rebellions that it would be easy target. However, after Han made a strong show of force, South Xiongnu submitted again and would not become a trouble spot for the rest of Han Dynasty.
In 110, Empress Dowager Deng's mother Lady Yin died. Her brothers resigned their posts to observe a period of mourning for three years, and after initially not approving the request, she eventually did, under female scholar Ban Zhao's suggestion. Even though they were without major government posts, however, they remained powerful advisors. As the years went by, Empress Dowager Deng's original humble nature appeared to entirely wear away as she hang onto power, and when some of her relatives and close associates suggested that she transfer the authorities to Emperor An, she became angry at them and would not do so.
In 121, Empress Dowager Deng died and was buried with her husband Emperor He with full honors. Emperor An finally took power at age 28. His wet nurse Wang Sheng (王聖) and trusted eunuchs Li Run (李閏) and Jiang Jing (江京), who had waited for years to have power, falsely accused Empress Dowager Deng of having considered deposing Emperor An and replacing him with his cousin, Liu Yi (劉翼) the Prince of Hejian. In anger, Emperor An removed all of Empress Dowager Deng's relatives from government and forced many of them to commit suicide. Later that year, however, he partially reversed his orders, and some of Empress Dowager Deng's relatives were allowed to return, but the clan had been decimated by then.