Milton “Mitch” R. Smith, III was born in El Paso, Texas, and spent his childhood in Texas, Iowa, and West Virginia. He received his B.S. degree in 1986 from Caltech, where he carried out research with Professor Terrence. J. Collins. After graduation, Mitch spent the summer as a research intern at Monsanto, Co. before beginning his graduate studies under the tutelage of Professor Gregory L. Hillhouse at the University of Chicago. At Chicago, his thesis work centered on the synthesis and reactivity of metal diazene complexes. After receiving his Ph. D. in 1990, he was awarded a Miller Fellowship at the University of California, Berkeley, where he spent two years synthesizing and exploring the reactivity of early transition metal oxo and imido complexes in the laboratories of Professor Richard A. Anderson. In 1992, Smith began his independent career and Michigan State University as an Assistant Professor in the Chemistry Department. There he built began a research program centered on the reactivity of transition metal complexes with organoboron reagents. He was promoted to Associate Professor with tenure in 1997 and Full Professor in 2002.

In 1999, Professor Smith and his graduate student, Carl Iverson, reported a thermal, catalytic synthesis of an organoborane from a borane and a hydrocarbon where the sole byproduct was hydrogen gas.  This landmark in C–H bond functionalization led to a family of highly efficient iridium catalysts that operate on a wide variety of aromatic and heteroaromatic compounds. Smith co-founded BoroPharm, Inc. with MSU colleague Professor Robert E. Maleczka, Jr. and CEO Todd Zahn. In 2008, Smith was a co-recipient of an award from the Presidential Green Chemistry Challenge Award for his contributions to C–H functionalization. In addition to C–H functionalization, Smith's research interests include polymer nanomaterials and energy storage and conversion.