Wisley was founded by Victorian businessman and RHS member George Ferguson Wilson, who purchased a 60 acre (243,000 m²) site in 1878. He established the "Oakwood Experimental Garden" on part of the site, where he attempted to "make difficult plants grow successfully". Wilson died in 1902 and Oakwood (which was also known as Glebe Farm) was purchased by Sir Thomas Hanbury, the creator of the celebrated garden La Mortola on the Italian Riviera. He gave both sites to the RHS the following year. Since then Wisley has developed steadily and it is now is a large and diverse garden covering 240 acres (971,000 m²). In addition to numerous formal and informal decorative gardens, several glasshouses and an extensive arboretum, it includes small scale "model gardens" which are intended to show visitors what they can achieve in their own gardens, and a trials field where new cultivars are assessed.

The laboratory, for both scientific research and training, was originally opened in 1907, but proved inadequate. It was expanded and its exterior was rebuilt during World War I. It was designated a Grade II Listed building in 1985.