Gelbart's early interest in science was inspired by his time as an undergraduate researcher in the molecular spectroscopy group of William Klemperer at Harvard. As a graduate student at the University of Chicago, with his mentors Stuart A. Rice, Karl Freed, and Joshua Jortner, he developed the modern theory of non-radiative processes ("radiationless transitions") in molecular photophysics. He was a US National Science Foundation/NATO Postdoctoral Fellow at the, University of Paris in 1971, and a Miller Institute Postdoctoral Fellow at UC Berkeley in 1972, during which time he switched fields and formulated a general theory of collision-induced optical properties of simple fluids.
He was appointed Assistant Professor of Chemistry, at UC Berkeley in 1972, continuing his researches on the quantum mechanical theory of molecular spectroscopy and on the statistical mechanical theory of intermolecular and multiple light scattering in liquids away from and near their critical points. He  moved to UCLA as Associate  Professor of Chemistry in 1975, and was promoted to full Professor in 1979 and to Distinguished Professor in 1999. He was Chair of the Department of Chemistry and Biochemistry at UCLA from 2000-2004 and has been a member of  UCLA's  California NanoSystems Institute since 2004 and of its Molecular Biology Institute from 2008.
At UCLA he  became a leader in the then-emerging fields of "complex fluids" and " soft matter physics". Shortly after moving there he began a 40-year collaboration with Avinoam Ben-Shaul on statistical-thermodynamic models of liquid crystal systems, polymer and polyelectrolyte (in particular, DNA) solutions, and colloidal suspensions, and on the self-assembly theory of micelles, surfactant monolayers, and biological membranes.
During a sabbatical year in 1998-99 at the Institute for Theoretical Physics in UC Santa Barbara and at the Curie Institute in Paris, Gelbart became deeply intrigued by viruses and over the course of the next several years, with his UCLA colleague Charles Knobler, established a laboratory to investigate simple viruses outside their hosts and isolated in test tubes. Early results included: the first measurement of pressure inside DNA viruses, establishing that it is as high as tens of atmospheres depending on genome length and ambient salt concentrations; and the demonstration that capsid proteins from certain viruses are capable of complete in vitro packaging of a broad range of lengths of heterologous RNA. This work, along with that of several other groups in the United States and Europe, helped launch the  field of "physical virology". Most recently he moved his viruses from test tubes to host cells, and from wildtype viruses to artificial viruses and virus-like particles, engineered for purposes of delivering self-replicating RNA genes, RNA vaccines, and therapeutic microRNA to targeted mammalian cells.