Robert D. Wells was born in Uniontown, Pennsylvania. He attended the University of Pittsburgh School of Medicine, where he earned a Ph.D. in 1960. During that time, he synthesized the first analog of the adrenocorticotropic hormone. He then did postdoctoral studies in the laboratory of H. Gobind Khorana where he participated in solving the genetic code. In 1966, Wells became an assistant professor in the Department of Biochemistry at the University of Wisconsin-Madison and rose through the ranks to full professor. In 1980, when he moved to the University of Alabama at Birmingham Schools of Medicine and Dentistry to be chairman of the Department of Biochemistry. In 1990, Wells became the founding director of the Institute of Biosciences and Technology at Texas A&M University in the Texas Medical Center in Houston.
Wells has investigated the molecular biology, genetics, and chemistry of DNA. He demonstrated that breakpoints of genomic rearrangements coincide with non-B DNA conformations, and that these rearrangements are the basis of a number of gene mutations that cause diseases. Throughout his career, he pioneered the concept that the long DNA helix is not a single monotonous conformation but consists of a number of non-B structures along the chain depending on the local sequence of base pairing. Wells was the first to report bent DNA, left-handed DNA, nodule DNA (a bitriplex), flexible and writhed DNA, and sticky DNA. He also codiscovered cruciforms (fourway functions) and made numerous discoveries regarding left-handed Z-DNA and triplexes.
Wells was president of the American Society for Biochemistry and Molecular Biology from 2002 to 2002 and the president and chairman of the board of directors of the Federation of American Societies for Experimental Biology (FASEB) from 2003 to 2004. He organized the Coalition of American Scientific Society Presidents, consisting of the presidents of the American Physical Society, the American Mathematical Society, the American Chemical Society, and FASEB. He was an associate editor for the Journal of Biological Chemistry for 13 years. He holds the Robert A. Welch Endowed Chair in Chemistry at the Institute of Biosciences and Technology and a Texas A&M University Regents Professorship.