A train carrying 900 passengers left from Yichang City, central Hubei Province for Chongqing in Wanzhou district.
It took seven years and about 50,000 workers to drill 159 tunnels, build 253 bridges through a stretch of mountains on the eastern edge of the Yunnan-Guizhou Plateau to complete the 377 km route.
The length of track that runs through bridges and tunnels accounted for about 74 per cent of the line's total track, official media here reported.
In the most extreme case, it took almost six years to drill a tunnel through Qiyue Mountain due to complex and dangerous geological conditions.
The line is also China's most expensive railway in terms of cost per km.
It cost about $9.01 million to build each km, compared with $4.35 million per km of the Qinghai-Tibet
The Yichang-Wanzhou railway will cut trips between Chongqing and Wuhan, capital of Hubei, from 22 hours to just five hours.
Travel time from other central or east China cities to southwest part of the country will also be significantly shorter, bringing new opportunities for residents who live in the steep and remote mountains.
China has invested heavily in railways connecting length and breadth of the country, including remote areas like Tibet with railway lines.
The railway in the country is also undergoing transformation to shift to high speed railway networks with the trains logging speed upto 486 km, setting new records.