The Oxford to London Paddington line suffered the equivalent of more than one signal problem every day last year.
New figures obtained by BBC Radio Oxford through a Freedom of Information request reveal 411 signalling problems during the 2014/15 financial year.
They also show a 22% increase in faults from 2012/13, which has drawn criticism from commuters faced with rising prices.
Network Rail blamed a lack of railway investment for the increase.
Signalling systems can fail for a number of reasons, such as power cuts or blown fuses, which cause signals to turn black and drivers to stop their trains.
A spokeswoman said the age of the equipment was the cause of the problems.
"We are replacing all of the signalling equipment along the Western route as part of our £7.5bn modernisation programme," she said.
During the 2013/14 financial year there was 379 signal problems and in 2012/13 the number was 337.
Sim Harris, the managing editor of Railnews magazine, said the signalling problems were causing "major disruption to thousands of people".
He said: "The problem with the signalling between Oxford and Reading, which is where these problems do occur, is that it's getting on [in age]."
'Taken for a ride'
Simon Stevenson, 42, from North Oxford, is a company director and commutes into London two or three times a week.
He said: "There seems to be a disconnect. We have constant increases in fares, but that doesn't translate into improvements in service."
A similar view was shared by Damian Fantato, 26 - a journalist who commuted into London from Oxford every day until earlier this year.
"Commuting to London costs an arm and a leg, so when you are delayed most mornings because you are sat somewhere just outside Reading it feels like you are being taken for a ride," he said.