While still at Harvard, Wennberg developed advanced airborne sensors to measure radicals in the atmosphere, in particular the odd-hydrogen 
radicals OH and HO. The laser-induced fluorescence instrument that he developed was placed in the nose of a  NASA ER-2 aircraft to measure radicals during flight. It has been used to measure radicals in both the troposphere and the stratosphere.
Wennbergs sensor was used in several NASA missions, beginning with the SPADE mission in 1993. SPADE obtained the first simultaneous in situ measurements of OH, HO, NO, NO, ClO, and BrO from the lower stratosphere. The data were used to calculate ozone loss rates and showed that HO dominated stratospheric ozone loss, a result that had not been previously observable. NASAs ASHOE/MAESA mission (1994) took measurements of HO from latitudes of -70°S to 70°N, reaching nearly from the south pole to the north pole. The STRAT mission (1995–1996) was the first to record measurements of HO in the upper troposphere, and demonstrated that the concentration of HO considerably exceeded expected levels.  The POLARIS mission in 1997 obtained measurements all the way to 90° N latitude, the North pole. As of 2004, Wennberg's instrument was modified for in situ measurements of water vapour and its Isotopologue HDO, and became the basis of the Harvard "Hoxotope".
Since his move to Caltech, Wennberg has been deeply involved in two inter-related long-term instrumentation and data-collection projects: the Orbiting Carbon Observatory, and its ground-based counterpart, the Total Carbon Column Observing Network. Goals include better understanding of the carbon cycle, validation of data from space-based instruments, and establishing a standard for ground-based in situ networked data collection.
In 2002, Wennberg was elected chair of the Total Carbon Column Observing Network (TCCON). In 2004, the first TCCON site was established.  The Total Carbon Column Observing Network is a group of about 20 ground-based sites worldwide that host Fourier transform spectrometers. The spectrometers examine near-infrared (NIR) solar absorption spectra and measure atmospheric column abundances of CO, CH, CO, NO and other molecules in terrestrial ecosystems.  Data enables researchers to identify and study local carbon "sources" and "sinks", and by pooling data across the system, to better understand mechanisms of carbon exchange involving the atmosphere, the land, and the ocean. Data from the sites is used to understand carbon dynamics and to validate data from space-based measurements of atmospheric CO and CH. Both terrestrial and atmospheric data are used to study carbon transfer within the atmosphere. Methane emissions from the Aliso Canyon gas leak were detected by TCCON within a day of the start of the leak. "TCCON has pioneered a key element of the ground segment measurements required to provide the evidence base for policy making for the next 100 years."
Wennberg is a founding member of the Orbiting Carbon Observatory and its successor, the Orbiting Carbon Observatory-2.  The first satellite failed to separate from the Orbital Taurus XL rocket used as its launch vehicle on February 24, 2009, and was destroyed during reentry.  The second satellite, a near duplicate, was launched successfully  by NASA on July 2, 2014, using a ULA Delta II 7320-10C rocket.  Spectrometers on the satellite can map the distribution of CO particles across the planet by measuring the average amount of CO above specific locations.
Wennberg is the principal investigator for the development of the Mars Atmospheric Trace Molecule Occultation Spectrometer (MATMOS), a collaboration between Caltech and the Canadian Space Agency with NASA support. MATMOS will be flown on the ExoMars Trace Gas Orbiter and take spectra of the sunlight through Mars atmosphere as the spacecraft goes through its orbital sunrise and sunset. MATMOS will be able to measure trace gases in Marss atmosphere at a concentrations of parts per trillion.