During the Reconstruction Era after the Civil War, most evangelical denominations in the North, especially the Methodists, were initially strong supporters of radical policies that favored the Freedmen (former slaves) and distrusted the Southern whites.

However, by the late 1860s in border state conferences, the MEC North moved well away from their work with the Freedmen's Bureau and often sided with the grievances of Southern white members.

Simpson was appointed Professor of Natural Science and elected vice-president of Allegheny College, Meadville, Pennsylvania.

Simpson was then elected editor of the Western Christian Advocate, which he made a strong temperance and anti-slavery organ, from 1848 to 1852.

In discharging his duties, Bishop Simpson visited and presided over conferences in all of the states encompassing the M.E.

From Berlin, Bishop Simpson extended his travels through Turkey, the Holy Land, Egypt, and Greece, returning to the United States in 1858.

In 1859, Bishop Simpson changed his residence from Pittsburgh to Evanston, Illinois, where he accepted the position of president of the Garrett Biblical Institute (now, Garrett–Evangelical Theological Seminary).

Before the Civil War, debates over slavery were highly contentious among Northern Methodists, but Simpson did not take sides, playing instead a moderate and cautious role.

[3] Simpson became a trusted friend of President Abraham Lincoln, who considered his advice of great value.

[4] During the War, Bishop Simpson delivered a number of speeches in behalf of the Union.

He was urged by the Secretary of War to undertake the organization of the freedmen at the establishment of the Freedman's Bureau.

After the war, Bishop Simpson was invited by President Grant to go as a commissioner to San Domingo but he declined both offers.

Bishop Matthew Simpson was taken ill at San Francisco in 1880, but recovered to preach the opening sermon at the First Ecumenical Methodist Conference in London (1881).

He died June 18, 1884, in Philadelphia and was buried in West Laurel Hill Cemetery, Bala Cynwyd, Pennsylvania.