The 32-container train, around 600 metres long, left the vast London Gateway container port laden with whisky, soft drinks and baby products, bound for Yiwu on the east coast of China.
It was seen off on its 18-day, 12,000-kilometre (7,500-mile) journey with a string quartet, British and Chinese flags, and speeches voicing hope that it will cement a new golden age of trade between the two countries as Brexit negotiations loom.
The rail route is cheaper than air freight and faster than sea freight, offering logistics companies a new middle option.
After the last three containers were lifted onto the wagons, the driver gave a thumbs-up and tooted his horn as he got the train rolling at the port in Stanford-le-Hope, east of London.
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"Restoring the ancient Silk Road as a means by which China, north Europe and now the UK can exchange goods is an important and exciting initiative," said Xubin Feng, the chairman of Yiwu Timex Industrial Investment, which is co-running the service.
The train will go through the Channel Tunnel before travelling across France, Belgium, Germany, Poland, Belarus, Russia and Kazakhstan before heading into China.
The containers, which also contain vitamins and pharmaceutical products, will be taken off and put on different wagons as they leave Poland, as the former Soviet Union countries use a wider rail gauge.
The containers switch back to standard gauge wagons at the Chinese border, an operation that typically takes around two hours.
London was hailing the first export train as part of its "global Britain" plan, recalibrating its post-EU trading outlook.
Rupert Soames, Prime Minister Theresa May's business ambassador for infrastructure and transport, told AFP that the new route was "positive and timely".
"I genuinely think that this is quite an historic day," said Soames, a grandson of World War II prime minister Winston Churchill.
"In some quarters now, globalisation is seen as a bad word. But here you see trade in all its glory and possibilities."
Some 13.5 billion pounds of trade headed to China, according to UK government statistics, with an average annual growth rate of 12.9 percent since 2006.
In terms of imports, China is Britain's third-biggest market after Germany and the United States, with trade worth 35.8 billion pounds last year.
The freight train is part of China's "One Belt, One Road" programme announced in 2013, reviving the ancient Silk Road trading routes to Europe.