During his reign, the Northern Qi's imperial administration was plunged into severe corruption and wastefulness, with the military suffering after Gao Wei killed the great general Hulü Guang in 572.
In 565, with astrological signs indicating that the imperial position should be changed, Emperor Wucheng's favored officials He Shikai and Zu Ting, wanting to ingratiate themselves with Empress Hu and Gao Wei as well, suggested that Emperor Wucheng avoid the ill fortune by passing the throne to Gao Wei.
Around the year 569, Emperor Wucheng suffered a major illness and died suddenly, after entrusting the important matters to He Shikai.
Lady Lu, who was also Consort Mu's adoptive mother, wanted Gao Heng to eventually be crown prince and emperor, but was afraid that Empress Hulü would oppose the plan, so she gave Gao Heng to Empress Hulü for her to raise.
In winter 570, Hulü Guang launched a counterattack and captured significant amounts of territory north of the Fen River (汾水, flowing through modern Linfen, Shanxi).
On his way back to the capital Yecheng (鄴城, in modern Handan, Hebei), Gao Wei ordered his troops demobilized even though many of the soldiers had not received rewards.
Hulü Guang submitted a secret petition to Gao Wei, requesting the emperor to send imperial messengers to the army to honor the soldiers.
Gao Wei did not act immediately, however, and the army approached Yecheng without receiving any words from the emperor.
Once, when he was resting at a governmental building, Zu, who had blinded during a period of imprisonment during Emperor Wucheng's reign, rode past him without realizing that Hulü was there, and never got off the horse as demanded by customs of the time.
However, Lady Lu did not relent in her hopes of making Consort Mu empress, stating to Gao Wei, "How can a son be crown prince and a mother be a servant girl, a concubine?"
They retained a group of literarily-capable men and authored one of the great compendia of the era, the Xiuwendian Yulan (修文殿御覽).
In summer 573, rival Emperor Xuan of Chen launched a major attack across the Yangtze River, commanded by the general Wu Mingche.
Gao Wei went against the advice of the officials Wang Hong (王紘), who advocated passive resistance while reducing tax burdens to strengthen the people's resolve, and Zhao Yanshen, who advocated commissioning the Liang dynasty general Wang Lin, who had long wanted to reestablish Liang at Chen's expense, with an army.
Wang, who accompanied Wei as a consultant, was then ordered to go to Shouyang (壽陽, in modern Lu'an, Anhui) to defend that city against attack—but with severe limitations on his authority.
All of Northern Qi's territory between the Yangtze and the Huai River fell into Chen control.
Despite the losses, however, Mu Tipo and Han advocated continued epicurean lifestyle on Gao Wei's and their own parts, with Mu famously stating, "Even if we lost all territory south of the Yellow River, we can still be like Qiuzi (龜茲, a city state in modern Xinjiang).
But what is more piteous is that a human life is like borrowed time, and we should use all this short period to seek pleasure.
Gao Wei was intending to visit the secondary capital Jinyang (晉陽, in modern Taiyuan, Shanxi), which he and his predecessors did on a regular basis.
During the meantime, however, Chen forces, commanded by Wu, commenced a new attack, putting Pengcheng (彭城, in modern Xuzhou, Jiangsu) under siege.
Gao Wei gathered his troops and headed for Pingyang, and Emperor Wu, believing Gao Wei's troops to be still strong, withdrew but put the general Liang Shiyan (梁士彥) in charge of defending Pingyang against the Northern Qi counterattack.
The Northern Qi forces sieged Pingyang with all effort—and after several days, were able to breach the wall—but at this point, Gao Wei stopped his attack and summoned Consort Feng so she could witness the fall of the city.
When Northern Zhou forces arrived at Jinyang, he left Jinyang under Gao Yanzong's command and fled, initially intending to flee to Shuo Province or Tujue, but after persuasion by the general Mei Shenglang (梅勝郎), headed back to Yecheng, accompanied by Gao Anagong.
His mother Lady Lu committed suicide, and his family members were all either executed or sentenced to hard labor.
Meanwhile, Tang Yong, still at Jinyang, along with other generals, persuaded Gao Yanzong to take the throne himself—stating to him that if he did not, they could not die for him.
Once Gao Wei arrived at Yecheng, he ordered that high rewards be posted for people who would join the army, but he himself was unwilling to contribute treasures from his own palace holdings.
He left the general Murong Sanzang (慕容三藏) in charge of Yecheng and fled toward Ji Province (濟州, roughly modern Liaocheng, Shandong), where had earlier sent Grand Empress Dowager Hu, Empress Dowager Mu, and the emperor Gao Heng.
Once Gao Wei left, Murong Sanzang was unable to defend the city, and it fell.
However, instead of delivering the edict and the imperial seals to Gao Jie, Hulü surrendered to Northern Zhou.
Gao Wei quickly tried to flee, but was captured by the Northern Zhou general Yuchi Qin (尉遲勤) and delivered back to Yecheng, to Emperor Wu.
He also ceremonially offered Gao Wei and the other captives to the ancestors at the ancestral temple, but did not harm them at this point.