She is the daughter of theologian and former Catholic priest Huub Oosterhuis and violinist Jozefien Melief of the Amsterdam Promenade Orchestra.

In 1990, Oosterhuis formed the band Total Touch with her brother Tjeerd and, in 1991, they participated in the Grote Prijs van Nederland, the most important amateur musician contest in the Netherlands.

The first single, "Touch Me There", became a summer hit and went Platinum, selling over 100,000 copies in its first month[2] - despite only peaking the Dutch charts at number 14.

Trijntje personally has a fondness for jazz instead of pop ballads, and, in 2004, she therefore signed a record deal with Blue Note and released the live album Strange Fruit, consisting of Billie Holiday and George Gershwin covers.

In 2008, she released a CD and DVD of an acoustic concert performance with guitarist Leonardo Amuedo, entitled Ken Je Mij (Do You Know Me).

A year later, in January 2012, Dutch singer Anouk made two videos of her and Trijntje working together in a studio, available through Twitter and Facebook.

In 2012, Oosterhuis replaced Angela Groothuizen as a coach on the third season of The Voice of Holland alongside Nick & Simon, Roel van Velzen and Marco Borsato.

Between 2012 and 2017, Oosterhuis was a member of Ladies of Soul, a supergroup completed by Candy Dulfer, Glennis Grace and sisters-in-law Berget Lewis and Edsilia Rombley.

In June 2017 Oosterhuis announced her departure from the Ladies of Soul to focus on her solo-career; she did return as a special guest during the 5th anniversary-shows on 23 and 24 March 2018.

In March 2019, Oosterhuis released the first single from her forthcoming album Dit is voor mij (This is for me); the same month she played a 25th anniversary-concert in a sold out Ziggo Dome.