As of 2017, the neighborhood is undergoing gentrification. They have since been replaced by large numbers of Hispanics and African Americans.

In the late 1960s, the residents of Highbridge were predominantly of Irish, Italian and Eastern European Jewish descent. In the early 20th century, the neighborhood was served by the Anderson–Jerome Avenues station, which connected the New York City Subway's Ninth Avenue elevated Line with the IRT Jerome Avenue Line ( 4 train). Around the turn of the 20th century, many of these estates were subdivided for urban development, however a few older houses still remain. Merriam, Anderson Avenue and Woodycrest Avenue for the Anderson family, and Shakespeare Avenue for the Shakespeare Garden on the Marcher family estate. The names of these families and their estates are reflected in the names of Highbridge's north-south avenues: Ogden Avenue and Boscobel Place for William B. In the mid-late 19th century, the area was developed as a suburban retreat for the elite, who built large homes overlooking the Harlem River. The bridge was closed to pedestrian traffic in the 1970s in the middle of the fiscal crisis affecting the city, and allowed to fall into disrepair in 2015 a reconstruction project was undertaken and completed with the opening of the bridge in 2019. Use of the structure to deliver water to Manhattan ceased in 1949. In 1864, a walkway was built across the High Bridge.

The structure originally carried Croton Aqueduct water across the Harlem River. The neighborhood takes its name from the High Bridge, built in 1848 by Irish immigrants. They called the hill that is now Highbridge 'Nuasin,' or 'the land between,' for its location between the Harlem River and an estuary that formerly flowed in the area of modern-day Jerome Avenue. At the time of European settlement, the southern Bronx was inhabited by the Siwanoy, a tribe of the Wappinger confederacy.

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