Why urban neighborhoods change and which policy interventions can be effective in halting the decline of incomes and housing quality in urban neighborhoods are questions that have interested urbanists for many decades since the historic changes that started sweeping through the American urban system after World War II. The diverse answers to the question of why change takes place have informed many decades of policy toward cities. The consensus view of the dynamics of neighborhood change focuses on long-run processes of decline and then renewal in the housing stock. This paper offers an initial look at the macroeconomic and spatial impact of the decline of manufacturing on neighborhood change in the context of 27 midsize cities in New England that had populations ranging from 47,000 to 207,000 in 1960. Some cities, such as New Bedford, Fall River, and Holyoke, Massachusetts, have lost population continuously since World War II. Others, such as Lawrence and Worcester, Massachusetts, and Waterbury, Connecticut, have experienced varying degrees of economic and population recovery after a few decades of population loss. Almost all of the cities have a legacy of spatially concentrated abandoned factory space that once provided employment to thousands of workers who were living in nearby neighborhoods. Using a new georeferenced data set of manufacturing employment in the early 1960s, a new block-level data set on housing for 1960 and 1990 within constant geographies, and census-tract data on median rents and housing values for 1960 through 2010, the study finds that macro shocks of declines in manufacturing employment prompted at the most a modest decline in rents and exerted no appreciable impact on averages of housing values citywide. The impact of the loss of manufacturing employment on neighborhoods was spatially concentrated. Housing values (but not rents) in the areas of cities that once had access to thousands of jobs in manufacturing fell substantially through 2000. The relative decline in housing values in the neighborhoods most affected by the manufacturing legacy meant that for a given level of housing quality (and value), the market demanded a higher stream of rental income.