After secondary school he graduated from Ghent University in 1969 as civil, mechanical and electrical engineering (Dutch: Burgerlijk Werktuigkundig en Elektrotechnisch ingenieur).

[5][4] In December 1974 he started working at CERN as a Fellow in the Proton Synchrotron (PS) division, participating in the renovation project of the control system of the accelerator.

[9] Cailliau later became a key proponent of CERN's web activity, running several student projects to create and support browsers on different operating systems including various UNIX flavours and Classic Mac OS.

[10] With Nicola Pellow he helped develop the first web browser for the Classic Mac OS operating system called MacWWW.

Cailliau was an active member of Newropeans, a pan-European political movement for which he and Luca Cominassi drafted a proposal concerning the European information society.