The city of Manchester is the regional capital and commercial, educational, medical and cultural centre of England's northwest region, the second largest economic region in the United Kingdom (UK) after London. Manchester is internationally known as the first city of the Industrial Revolution. This chapter explores the knowledge economy strategies of Manchester. It analyses the foundations of the knowledge economy for Manchester. They include the knowledge base, the economic base, the quality of life, the accessibility, the urban diversity, the urban scale, and the social equity in the city. The chapter discusses Manchester's knowledge economy activities. It explains how well the city (and the actors in it) manages to: attract and retain talented people; create new knowledge; apply new knowledge and make new combinations; and develop new growth clusters. The chapter contains conclusions and unfolds perspectives for Manchester's position in the emerging knowledge economy.