Members voted by 498 to 114 to support the European Union (Notification of Withdrawal) Bill.
This gives the government the parliamentary approval necessary to trigger Article 50, which gives the EU member-states a two-year period to withdraw.
The government was forced to bring in legislation before Parliament following a Supreme Court verdict last month, which held that the executive’s prerogative was not sufficient.
While MPs of different parties may attempt to bring amendments to the Bill at later stages, the government is likely to be able to keep to its Brexit timetable.
With Labour and the Conservative party backing legislation, it fell to rebels and other parties to oppose the Bill.
While many Conservatives have been critical of the government’s approach in the run-up to legislation, opposition within the party melted away.
Only Ken Clarke, a former Conservative Chancellor of the Exchequer, to oppose the Bill at its second reading.
Former Chancellor George Osborne, warned of a constitutional crisis if the House did not pass legislation.
Labour’s position - which has been to support legislation, but push for reforms to ensure single market access and protections for workers - has drawn criticism from across parties.
The vote is, of course, not the end of the road.
Legislation will now have to pass to the committee stage where amendments to legislation will be considered and then voted on.