The House of Commons backed the agreement, struck between Prime Minister Boris Johnson and the EU on Christmas Eve, by 521 votes to 73.
The deal, which stretches to 1,246 pages and covers £660bn worth of trade, will now pass to the House of Lords to be considered by peers.
The government is hoping the agreement will pass through all of its required parliamentary stages in a single day on Wednesday.
And, therefore, it will be fully ratified ahead of the end of the Brexit transition period at 11pm on New Year’s Eve.
Prime Minister Boris Johnson, who was due to formally sign the agreement in Downing Street on Wednesday afternoon, earlier told MPs the deal would allow the UK to take control of its “national destiny”.