A passenger leaves the first Eurostar train to arrive at St Pancras
The high-speed train left the restored £800m station as scheduled at 1103 GMT on Wednesday.
It arrived in Paris just over two hours later at 1317 GMT via the newly completed £5.8bn Channel Tunnel rail link, now known as High Speed 1.
Protesters who are against the station's re-development demonstrated as the service pulled out.
One group representing residents who live nearby claim London's poor are being "squeezed out" of the area.
The London Cycling Campaign has also complained the access to the station for bicycles is sub-standard.
And Greenpeace unfurled a banner on the front of St Pancras which supported the rail link but urged Prime Minister Gordon Brown not to expand Heathrow airport.
The first departures from St Pancras coincided with the start of an open-ended strike by French rail unions in protest at President Nicolas Sarkozy's planned pension reforms.
But Eurostar was confident it would not impact on services.
Eurostar chief executive Richard Brown and Friends of the Earth executive director Tony Juniper named the first train Tread Lightly - after a Eurostar environmental campaign began earlier this year.
The company has set a target of reducing its carbon dioxide emissions by 25% per passenger journey by 2012.
Mr Brown said: "Today marks a new dawn for short-haul travel in Europe.
"Our move to St Pancras makes Eurostar even more accessible to travellers across Britain.
RAIL DESTINATIONS Fastest travel times London to Avignon: 5h 51m London to Inverness: 8h 08m Compare more times below
The first commercial passenger train for Brussels departed six minutes before the first arrival from the same city pulled into St Pancras, at 1109 GMT.
Work on the station began in 2001 to enable it to accommodate Eurostar trains as well as East Midlands Trains services, Thameslink and high-speed commuter services to Kent, due to start in 2009.
The new route will cut journey times to Paris by 20 minutes to two hours and 15 minutes, and to Brussels by 25 minutes to one hour and 51 minutes.
The last Eurostar train left London Waterloo at 1812 GMT on Tuesday.
Interior of the newly refurbished station 
Eurostar train services which link the United Kingdom with Europe via the Channel Tunnel have moved to a new London terminal. The first services from St Pancras International launched today following the completion of the Channel Tunnel Rail Link which promises to reduce journey times to Europe by 20 minutes.

The Channel Tunnel Rail Link, to be branded as High Speed 1, has been built in two phases; the first section was completed in 2003 and the second section was brought into use today. 

Eurostar chief executive Richard Brown said: "Today marks a new dawn for short-haul travel in Europe. Our move to St Pancras makes Eurostar even more accessible to travellers across Britain. We will carry passengers with greater speed, ease and reliability than ever before, and our travellers will have the extra reassurance of knowing that they are making far less environmental impact compared with flying." 

Waterloo railway station, the previous international London terminal, will be returned to domestic use following the move to St Pancras.