Based on data from the 1980s, Sassen’s influential book ‘The Global City’ interrogated how changes in the occupational structure affect socio-economic residential segregation in global cities. Here, using data for New York City, London and Tokyo, we reframe and answer this question for recent decades. Our analysis shows an increase in the share of high-income occupations, accompanied by a fall in low-income occupations in all three cities, providing strong evidence for a consistent trend of professionalization of the workforce. Segregation was highest in New York and lowest in Tokyo. In New York and London, individuals in high-income occupations are concentrating in the city centre, while low-income occupations are pushed to urban peripheries. Professionalization of the workforce is accompanied by reduced levels of segregation by income, and two ongoing megatrends in urban change: gentrification of inner-city neighbourhoods and suburbanization of poverty, with larger changes in the social geography than in levels of segregation.