Studying on his own, he gained a thorough knowledge of specific 17th- and 18th-century performance techniques and conventions of interpretation. This led to the introduction, in 1969, of a more authentic way of playing the violin, whereby the instrument was no longer held under the chin, but lay freely on the shoulder; this was to have a crucial influence on the approach to the violin repertoire and was consequently adopted by many players starting in the early 1970s.

From 1964 to 1972, Sigiswald Kuijken was a member of the Brussels-based Alarius Ensemble (with Wieland Kuijken, Robert Kohnen and Janine Rubinlicht), which performed throughout Europe and in the United States. He subsequently undertook individual chamber music projects with a number of Baroque music specialists, chief among which were his brothers Wieland and Barthold, Gustav Leonhardt and Robert Kohnen, as well as Anner Bylsma, Frans Bruggen and René Jacobs. In 1972, with the encouragement of Deutsche Harmonia Mundi and Gustav Leonhardt, he founded the Baroque orchestra La Petite Bande, which since then has given innumerable concerts throughout Europe, Australia, South America, China and Japan, and has made many recordings for a number of labels (including Deutsche Harmonia Mundi, Seon, Accent and Denon).

In 1986 he founded the Kuijken String Quartet (with François Fernandez, Marleen Thiers and Wieland Kuijken), which specialises in the quartets and quintets (with Ryo Terakado as first violist) of the Classical period. Recordings of quartets and quintets of Mozart and Haydn have appeared on Denon.

From 1971 to 1996, Sigiswald Kuijken taught Baroque violin at the Koninklijk Conservatorium in The Hague; since 1993 he has taught at the Koninklijk Muziekconservatorium in Brussels. In addition, he has for many years been in demand as a guest teacher at a number of institutions (including the Royal College of Music in London, Salamanca University and the Accademia Chigiana in Siena).

Since 1998, Sigiswald Kuijken occasionally conducts "modern" symphonic orchestras in romantic programms (Schumann, Brahms, Mendelssohn).