From their introduction the 901 Class 2-4-0s put in excellent service on the Newcastle-Edinburgh and Newcastle-York runs hauling 160-170 ton loads. During 1884 engines based at Gateshead depot were averaged 4,400 miles per month. Apart from minor instances of updating only two of the class underwent extensive rebuilding. More substantial modifications were made to the last of the Neilson-built engines. No. 933 which in 1907 was not only reboilered but converted into a 4-4-0 but was scrapped in 1914. It became one of 29 of the class withdrawn between 1913 and 1914 and, but for the onset of the first World War, the rest would have follow suit. Instead the curtailing of new construction led to a shortage of motive power and new work was found for the 901 Class. Some were drafted on to the coastal line between Scarborough and Bridlington but the majority were stationed at Darlington. From here they worked passenger services over the Stainmore route to Kirkby Stephen, Penrith and Tebay. Darlington also kept them on as pilots. By 1923 only ten of the class remained and the now preserved No.910 was amongst the final five to be withdrawn from service.
On 25 March 1877, locomotive No. 901 was hauling an express passenger train which was derailed at Morpeth, Northumberland due to excessive speed on a curve. Five people were killed and seventeen were injured.
On 4 October 1894, locomotive No. 904 was one of two locomotives hauling a sleeping car train which overran signals and collided with a freight train that was being shunted at Castle Hills, Yorkshire. One person was killed.