Drivers with Southern Railway have voted 4-1 to end the long-running dispute over driver-only trains, the Aslef union says.
The agreement means drivers will receive a pay rise of 28.5% over the next five years and be joined on-board on every train by a second employee with full safety training – other than in "exceptional circumstances".
It brings to an end a dispute that began in April last year, resulting in a series of strikes that have caused disruption for commuters, students and other passengers.
A number of false dawns have added to the frustration, most recently in August when talks aimed at ending the dispute stalled.
But Nick Brown, chief operating officer of Southern owners Govia Thameslink Railway (GTR), said that passengers could now look forward to "stability" and a "resilient and reliable service".
"This dispute has been difficult for our passengers in particular and we are pleased that we can now move ahead and deliver stability by finally concluding this deal with Aslef," he said.
"Our trains will be planned to have a second person on board and this has been the arrangement we have operated over the last year. More on-train staff are on more trains with more passengers than ever before. The on-board service concept has been welcomed by our passengers across the board.
"Should, in certain circumstances, a train not have that second person on board then it will still be able to run until a replacement can be provided. Avoiding cancellations is key to us delivering a resilient and reliable service across the busiest and most congested part of the UK rail network."
The deal has not been as well received by the Rail, Maritime and Transport (RMT) union, with general secretary Mick Cash insisting that its campaign would not change.
He described the agreement as "shoddy" and "appalling", adding that it "institutionalises discrimination against disabled and older people".
"Where such passengers who required assistance were once guaranteed a second member of staff to assist, a new clause in this deal deliberately sets out where there is no on-board supervisor the driver will knowingly have to leave such passengers stranded on trains and stations," he said.
"RMT believes that a significant factor in delivering this result was the threat of massive legal costs levied on the union by GTR as a result of the anti-trade union laws."