In his Lancet obituary in 1924, it was reflected that he was

the first to practice brain surgery in the modern sense of the word.

His surgical work was extensive and he was also successful in the field of bone surgery, and published a paper in 1881 on the innovatory surgery of bone transplantation. Later, in 1887, he developed a procedure, which became known as Macewen's osteotomy - breaking and reshaping children's leg bones, which had become deformed by rickets. His work on opening up the chest led to successful surgery of the lung and the development of a surgical means of curing inguinal hernia. His publications on these accomplishments established his international reputation as a surgeon.

In 1892, he took up the Regius chair of Surgery at the University of Glasgow, a position that allowed him to continue his research and teaching, where his influence on young students was notable. He was knighted in 1902, and received many honours both in Europe and the US.