Marsiling Secondary School was founded in 2001 amidst the shortage of secondary schools, especially in anticipation of the record-number of 2000 primary school graduates. Mrs Choy Chee Meh was appointed the first principal of MSL and land acquisition at the current site began shortly after the decision to establish the school. Primary school graduates had little interest in MSL during the early founding years, compared to the well-established secondary schools in Woodlands with deeply-rooted history.

Staff and students managed, however, to build up MSL's reputation through the bold attempt to engage new ideas and initiatives, such as the Apple-MOE Collaborations. MSL have significant reputation today throughout the region and MSL's intake have grown considerably since. Throughout the entire tenture of Mrs Choy, MSL won comparatively more award on the national level in academics and sports than established secondary schools in the region.

MSL was involved in the 3 years Apple-MOE Collaboration in which Apple Macintosh computers were introduced, and the application of the successful education model used in United States devised by educators and Apple Computer. Through the collaboration, MSL hosted 3 Edu-Pi camps, a 2 day educational workshop that encourage the use of lifestyle products from Apple such as iMovie and the Mac OS.

The school adopted the core values of P.R.I.D.E., which stood for Perseverance, Responsibility, Integrity, Diligence, and Enterprise respectively. A.C.H.I.E.V.E. was adopted as the school's core aims as Academic Excellence, Character Building, Healthy lifestyle, IT way of life, Excellence in Aesthetics, Valued relationships, and Enriching partnerships.

As similar with other schools, discipline have also posed as a minor issue within MSL. Vandalism and theft related problem shown slow growth over years. School disciplinary committees and teachers-in-charge of disciplinary issues were generally strict, and MSL retained her tough stand on late-coming students, thefts, vandalism and other associated disciplinary issues, while one of the toughest punishment used previously by the previous principal, such as public caning, was deemed unnecessary by the incumbent principal, and desisted the use of such penalty.