On his return to the United States, he became a professor of Oriental and biblical literature at Western Theological Seminary, Allegheny, Pennsylvania, and he held that chair from 1852 until his death in 1876.

Charles Hodge, William Henry Green, J. W. Alexander and others from Princeton Seminary said, "The excellent Commentaries of Dr. Melancthon Jacobus have deservedly attained a high reputation, and their wide circulation proves how well they are adapted to the wants of both ministers and laymen.

They present, in a brief compass, the results of extensive erudition, abound in judicious exposition and pertinent illustration, and are, moreover, distinguished by doctrinal soundness, evangelical character, and an eminently devout spirit."

William S. Plumer noted that Jacobus' commentaries were "characterized by solid learning, sound doctrine, and lucid statements, a pleasant style, and the most serious spirit of piety."

Regarding his work on Acts, Dr. Robert P. Martin showered praise with this comment: "Jacobus writes in the popular style of Albert Barnes, and is solidly Reformed.