This paper describes a microwave resonator incorporating microfluidic lab-on-chip sensor system capable of performing simultaneous differential measurement based sensing of liquid samples. The resonators are split-ring resonator shapes made of gold on glass substrates. Directly bonded on glass substrates are polydimethylsiloxane microchannels. Sensor system design incorporates a pair of identical resonators, one of which performs reference reading from the background. Tracking the difference of the responses of both resonators simultaneously, rather than a single one, is used to obtain a more linear and noise-free reading. The sensor system was produced with conventional fabrication techniques. It is compatible with low-cost, simple, easy to handle sensing applications. Results indicate that reliable differential measurement was possible owing to a well-matched pair of sensors with a response error as low as 0.1%. It was also demonstrated that differential measurement capability enables sensing with improved linearity. Measurements were performed with glucose solutions in the range of 3.2–16.1 mM, achieving a sensitivity of 0.16 MHz/mM.