His family was from Qin Commandery (秦郡, roughly the part of modern Nanjing, Jiangsu, north of the Yangtze River).
When the general Hou Jing rebelled and sieged the capital Jiankang in 548, Wu Mingche appeared to be at his home in Qin Commandery, which, as a result of trade routes' being cut off, suffered from a famine.
Wang Sengbian's lieutenant Chen Baxian was put in charge of the important city Jingkou (京口, in modern Zhenjiang, Jiangsu).
It was also around this time that Wu studied histories and other classical works, as well as astronomy and strategies from the official Zhou Hongzheng (周弘正).
In winter 554, Western Wei launched a major attack on Emperor Yuan's capital Jiangling (江陵, in modern Jingzhou, Hubei).
However, before Wang could even mobilize his troops, Jiangling fell, and around the new year 555, Western Wei forces put Emperor Yuan to death.
Wang, however, was subsequently defeated by Hou Tian (侯瑱), and both he and Xiao Zhuang were forced to flee to Northern Qi.
As part of Chen's effort to then take control of Xiao Zhuang's territory, Emperor Wen assigned Wu to be the governor of Wu Province (武州, roughly modern Changde, Hunan), but he was defeated by the Northern Zhou (Western Wei's successor state) general Heruo Dun (賀若敦) and forced to withdraw to Baling (巴陵, in modern Yueyang, Hunan).
Chen Xu consulted Mao Xi (毛喜) and Wu Mingche, both of whom persuaded him not to follow Yin's message.
Chen Xu therefore invited Liu to a meeting—and while the meeting was still going on, had Mao confirming with Empress Dowager Shen and Emperor Fei that it was not their order that he leave the palace.
Once Mao confirmed so, Chen Xu arrested Liu and ordered him to commit suicide, while demoting Dao to a lesser position.
Dao later tried to start an uprising with the general Han Zigao (韓子高), but the plot was discovered, and Chen Xu forced both of them to commit suicide.
In summer 567, Chen Xu commissioned Wu as the governor of Xiang Province and had him command a major part of the troops against Hua, along with general Chunyu Liang (淳于量).
Hua and the Northern Zhou general Yuwen Zhi (宇文直) were forced to flee to Western Liang's capital Jiangling.
In light of the victory, Wu first captured Western Liang's Hedong Commandery (河東, part of modern Jingzhou), and then further put Jiangling under siege.
Emperor Xuan decided to carry out attack, and because Chunyu Liang was the senior general, most officials believed that he should command the mission.
By fall 573, Wu had the important city of Shouyang (壽陽, in modern Lu'an, Anhui), defending by Wang Lin, under siege, and although he could not capture it quickly, he did when the Northern Qi relief force commanded by Pi Jinghe (皮景和) arrived but was hesitant to engage him.
The region between the Yangtze and the Huai was now entirely in Chen hands, and Emperor Xuan created Wu the greater title of Duke of Nanping.
In spring 578, the Northern Zhou general Wang Gui (王軌) arrived with a force to lift the siege, and he, as his first step, cut off Wu's supply route (and escape path).