We previously reported a noncontact ultrasound water jet indentation system for measuring and mapping tissue mechanical properties. The key idea was to utilize a water jet as an indenter as well as the coupling medium for high-frequency ultrasound. In this paper, the system was employed to assess articular cartilage degeneration, using stiffness ratio as an indicator of the mechanical properties of samples. Both the mechanical and acoustical properties of intact and degenerated bovine patellar articular cartilage (n = 8) were obtained in situ. It was found that the stiffness ratio was reduced by 44 ± 17% after the articular cartilage was treated by 0.25% trypsin at 37 °C for 4 h while no significant difference in thickness was observed between the intact and degenerated samples. A significant decrease of 36 ± 20% in the peak-to-peak amplitude of ultrasound echoes reflected from the cartilage surface was also found for the cartilage samples treated by trypsin. The results also showed that the stiffness obtained with the new method highly correlated with that measured using a standard mechanical testing protocol. A good reproducibility of the measurements was demonstrated. The present results showed that the ultrasound water jet indentation system may provide a potential tool for the non-destructive evaluation of articular cartilage degeneration by simultaneously obtaining mechanical properties, acoustical properties, and thickness data. ; Author name used in this publication: Y. P. Zheng ; Author name used in this publication: A. Mak ; Author name used in this publication: Q.-H. Huang ; Author name used in this publication: M.-H. Lu