Beginning in earth sciences at Harvard, Betts-LaCroix contributed to the field of long-term regulation of oxygen on Earth over multi-100 Million-year timespans, quantifying the effect of the burial efficiency of organic carbon as a feedback mechanism.

At MIT, he designed and built an autonomous, robotic system that enables research into ocean circulation patterns and climate change, by operating untended for up to one year at sea on battery power and collecting hyper-pure water samples at predetermined intervals.

In work at Caltech, Betts-LaCroix moved into biophysics, publishing a paper in Science that has been cited by more than 700 subsequent scientific works. In this work, he, along with David Beratan and José Onuchic proved for the first time that electron-transfer rates in proteins are determined by the electron orbital interactions in the protein structure.