A compact and portable open-path sensor for simultaneous detection of atmospheric N(2)O and CO has been developed with a 4.5 μm quantum cascade laser (QCL). An in-line acetylene (C(2)H(2)) gas reference cell allows for continuous monitoring of the sensor drift and calibration in rapidly changing field environments and thereby allows for open-path detection at high precision and stability. Wavelength modulation spectroscopy (WMS) is used to detect simultaneously both the second and fourth harmonic absorption spectra with an optimized dual modulation amplitude scheme. Multi-harmonic spectra containing atmospheric N(2)O, CO, and the reference C(2)H(2) signals are fit in real-time (10 Hz) by combining a software-based lock-in amplifier with a computationally fast numerical model for WMS. The sensor consumes ~50 W of power and has a mass of ~15 kg. Precision of 0.15 ppbv N(2)O and 0.36 ppbv CO at 10 Hz under laboratory conditions was demonstrated. The sensor has been deployed for extended periods in the field. Simultaneous N(2)O and CO measurements distinguished between natural and fossil fuel combustion sources of N(2)O, an important greenhouse gas with poorly quantified emissions in space and time.