Merrill was born in Minneapolis, Minnesota, and graduated from Stanford University in 1908. He obtained his PhD in 1913 from the University of California. After teaching at the University of Michigan from 1913 to 1916 and serving briefly with the US Bureau of Standards in Washington, he was appointed to the staff of the Mount Wilson Observatory in 1919, remaining there until his retirement in 1952.

It was in his retirement year that he detected the lines of technetium in the spectra of S-type stars, a class of cool red giant stars. This was surprising for the most stable isotope of technetium has a half-life of about 2.6 million years, which is much shorter than the lifetime of a star. Merrill thought it unlikely that there was an unknown stable isotope of technetium found only on S-type stars and argued rather that it was being produced within the stars by some form of nuclear reaction. The technetium lines are now accepted as strong evidence for one of the nuclear processes by which the heavy elements are thought to be created in the interiors of stars.