Trained at Rose Bruford College, Merrison has appeared in film, television, and in the theatre. He has been a member of the Royal Shakespeare Company. Onscreen appearances include Doctor Who and the film Heavenly Creatures.
Merrison has worked extensively in radio, being most famous for starring as Sherlock Holmes in the long-running BBC series, which ran from 1989 to 1998. Actor Michael Williams co-stared as Dr. John Watson.
Later, with Andrew Sachs as Watson (Williams had died in 2001), Merrison continued to play Holmes in the Bert Coules-scripted pastiche series The Further Adventures of Sherlock Holmes, the first series of which was broadcast in 2002, the second in 2004, the third in 2008-9 and the fourth in 2010. He is the only actor to have played Holmes in adaptations of every single Conan Doyle short story and novel about the character.