The cemetery in its original form—the northwestern wooded area—opened in 1839, as part of a plan to provide seven large, modern cemeteries, now known as the "Magnificent Seven", around the outside of central London. The inner-city cemeteries, mostly the graveyards attached to individual churches, had long been unable to cope with the number of burials and were seen as a hazard to health and an undignified way to treat the dead. The initial design was by architect and entrepreneur Stephen Geary.
On Monday 20 May 1839, Highgate (West) Cemetery was dedicated to St. James by the Right Reverend Charles James Blomfield, Lord Bishop of London. Fifteen acres were consecrated for the use of the Church of England, and two acres set aside for Dissenters. Rights of burial were sold for either limited period or in perpetuity. The first burial was Elizabeth Jackson of Little Windmill Street, Soho, on 26 May.
Highgate, like the others of the Magnificent Seven, soon became a fashionable place for burials and was much admired and visited. The Victorian attitude to death and its presentation led to the creation of a wealth of Gothic tombs and buildings. It occupies a spectacular south-facing hillside site slightly downhill from the top of the hill of Highgate itself, next to Waterlow Park. In 1854 the area to the east of the original area across Swains Lane was bought to form the eastern part of the cemetery. Both the cemeteries are still used today for burials, but these areas are closed to the public. Most of the open unforested area in the East Cemetery still has fairly few graves on it.
The cemetery's grounds are full of trees, shrubbery and wildflowers, most of which have been planted and grown without human influence. The grounds are a haven for birds and small animals such as foxes.
Because of the Karl Marx association a variety of Socialist leaders and thinkers are buried within the cemetery grounds.
Highgate Cemetery was featured in the popular media from the 1960s to the late 1980s for its so-called occult past, particularly as being the alleged site of the "Highgate Vampire".