Measurement of in-use emissions from heavy-duty (HD) vehicles under real-world operation has been widely performed by using portable emissions measurement system (PEMS). PEMS serve as an accurate and lightweight emissions measurement system to evaluate in-use emissions from HD vehicles. However, emissions measurement using PEMS instrumentation can be time consuming and labor intensive. Advantage of utilizing already existing on-board sensors such that they can potentially provide an alternative measurement methodology to the PEMS. A successful implementation of an on-board NOx sensor-based methodology for assessing in-use NOx emissions will allow for a cost-effective and simplified approach to monitor real-world, NOx emission rates. The technology of on-board NOx sensors is in its initial stages to be used to monitor in-use NOx emissions and the ability of the sensor to measure NOx concentration during selective catalytic reduction (SCR) activity period is of concern. Furthermore, the on-board NOx sensors are also subject to various cross-sensitivity and durability concerns. The primary objective of this dissertation is to compare the on-board NOx sensor response and accuracy against laboratory grade instrumentation that include PEMS using Non-Dispersive Ultra-Violent (NDUV) and Fourier transform infrared spectroscopy (FTIR) measurement to assess the measurement thresholds of on-board NOx sensors. The study compares the cross-sensitivity of the NOx sensors to ammonia (NH3) concentration in the exhaust. NH3 slip from SCR is believed to interfere with NOx measurements using Zirconium oxide sensors and this study will discuss NH3-NOx cross sensitivity on on-board NOx sensors during real-world HD vehicle activity. Results from this study will compare on-board NOx sensor measurement capabilities and they will be assessed at different power levels related to different SCR conversion efficiency and different NOx concentration levels related to measurements obtained from a laboratory grade emissions