She was a research assistant at Scripps Institution of Oceanography, at the New York Zoological Society, and at the American Museum of Natural History in New York. She was the founding director (1955 to 1967) of the Cape Haze Marine Laboratory in Sarasota, Florida, now a leading center for shark research called the Mote Marine Laboratory with which she is still affiliated. Her studies on the intelligence and behavior of sharks at this point earned her the nickname "Shark Lady".
Dr. Clark is the recipient of three honourary D.Sc. degrees and awards from the National Geographic Society, the Explorers Club, the Underwater Society of America, the American Littoral Society, the Gold Medal Award of the Society of Women Geographers, and the President's Medal of the University of Maryland. She has authored three books and over 160 scientific and popular articles.
She has conducted 71 deep submersible dives. Her latest research projects concern the behavior of tropical sand fishes and deep-sea sharks. These studies have been featured in 12 articles she has written for National Geographic magazine.