Forced to work his shift, Holmes called at the Otterington signal box before walking to Manor House. He asked the signalman there to notify him when his mother arrived on the train from York to look after his wife. He also told the Otterington signalman that he was already exhausted. It was night with a thick mist which later thickened to fog.
About three hours into Holmes's shift, two express passenger trains were due from the north, but the second had been delayed, and a goods train was sent down the main line after the first. Holmes let it into his section but then was "overmastered by sleep". The goods train came to a halt just outside his signal box. Thirteen minutes later, Holmes awoke, rather confused. The Otterington signalman warned him to be ready for the second express, and Holmes saw that his instruments still indicated that there was a train on the line. He had forgotten about the goods train, and thought he had fallen asleep before clearing the instruments after the first express. He cleared the instruments and accepted the second express.
The express crashed at sixty miles per hour into the goods train, which had only just started to move off at walking pace. Nine passengers and the guard of the goods train were killed, and 39 people injured. Nearly an hour later, hot coals from the firebox of the engine of the express train set the wreckage on fire. The express train's Pintsch oil gas lighting system acted as an accelerant and added to the fire. Two of the bodies were incinerated, and were not recovered.