Taoiseach Leo Varadkar and Minister for Transport, Shane Ross TD, attended the official commencement of the scheme on the N4 Collooney to Castlebaldwin Road.
The €150 million investment for the north West region is aimed at replacing a "notoriously dangerous" section of the route.
It was approved last month as part of the Project Ireland 2040 and the National Development Plan.
Welcoming the works, Minister Ross said: "Over the decades there have been many serious collisions and fatalities in this area. There are families and communities in the North West region who are still suffering the loss of loved ones who have died on this road. Many others have been seriously injured. After a fatality in 2015, this section was described by the County Coroner as 'possibly the worst road' in Ireland. This is not acceptable.
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"Good roads can save lives. On behalf of this Government and local representatives, I'm pleased that this road will now be rebuilt to a modern standard."
When completed, the work will enhance safety for road users by improving the road alignment and dividing traffic travelling on the N4/M4 between Sligo and Dublin.
Minister Ross added: "A better, safer road network leads to improvements in employment, education, healthcare and social cohesion- as well as saving lives.
"Nevertheless, no matter how good a road is, every motorist must take all necessary caution when driving a motorised vehicle- a lethal weapon. I appeal to all drivers to please keep to the speed limits, don't drink and drive, wear your seatbelt at all times and never use a mobile phone while driving. As we are warned that weather conditions are due to deteriorate this week, I cannot stress enough the importance of taking all necessary precautions while driving, cycling or walking along our roads."
(JG)
