The current site of New Place was initially within the plot of an Iron Age farmstead sometime around 700 BC – 43 AD, as indicated by pottery that also dates to the same time period.

New Place was built atop the site of a former 13th-century timber building in 1483 by Sir Hugh Clopton, a wealthy London mercer and Lord Mayor.

When John Leyland visited in 1540, he described New Place as a "praty house of Bricke and tymbre wherm he (ie Hugh Clopton) lived in his latter dayes and dyed".

In 1567 Bott sold New Place to William Underhill I (c. 1523 – 31 March 1570), an Inner Temple lawyer and clerk of assizes at Warwick, and a substantial property holder in Warwickshire.

[15][16][17] In 1756 then-owner Reverend Francis Gastrell (vicar of Frodsham, Cheshire[18]) having become tired of visitors, attacked and destroyed a mulberry tree in the garden said to have been planted by Shakespeare.

Clay pipe fragments unearthed in recent years in Shakespeare's Stratford-upon-Avon garden were found to possibly contain traces of cannabis, along with tobacco and camphor, based on the results of a study published in the South African Journal of Science.

[25][26] This has fuelled speculation by some that Shakespeare may have possibly smoked cannabis,[27] which is known to have been used to treat certain medical conditions at the time by Elizabethans, as well as in the manufacture of materials such as sails, rope, and clothing, and may have also been used for purposes of pleasure.

[25] The pipe fragments, however, could have belonged to any number of other persons besides the famous playwright, and cannot be definitively dated to the periods of his residency there as they could have been from the 18th century, around 200 years after Shakespeare's death.