The school was established in 1974.
In 2007 a house-based approach to student support was developed which includes "vertical" tutor groups, meaning that form groups have a mix of ages which encourages students to have stronger relationships with other members of the school, not exclusively their own year.
In 2017, the school removed the vertical tutoring system but decided to keep the current houses. After removing this system, there are only eight schools nationally that still use the vertical tutor system.
Most students join the school in year 9, aged 13. They start their GCSE courses in year 9 and take the GCSE exams in years 10 and 11, aged 15 or 16. Some students choose to continue attending the school following their GCSEs and join a large sixth form of over 420.
Between October 2003 and April 2006, the school underwent a major building and refurbishment programme as part of the Mid-Bedfordshire PFI scheme.
In November 2006, the Mid-Bedfordshire PFI scheme was officially opened by the Queen during a visit to Bedfordshire at neighbouring Samuel Whitbread Upper School.
Science College and Academy
In September 2006 the school gained specialist Science College status. The school continues to teach the full range of National Curriculum subjects, but uses its strength and expertise in Science and Mathematics to support other schools and the local community. The school has also been selected by the DfES and the Specialist Schools Trust to become a Deep Support Hub for the Eastern Region.
On 1 March 2012, Harlington Upper School officially became an academy.