For 16 years Sadoway taught 3.091 Introduction to Solid State Chemistry at MIT, one of the largest classes at MIT. Sadoway's animated teaching style was popular with students and freshman enrollment in the course steadily increased through 2010.
In the fall of 2007, the number of students registering for 3.091 reached 570 students, over half the freshman class. The largest lecture hall available on campus seats 566 students. Sadoway much preferred teaching in one of the smaller lecture halls, seating only 450; as such, the institute had to take the unprecedented step of streaming digital video of the lecture into an overflow room to accommodate all the students interested in taking the course. In contrast, most classes at MIT are relatively small with approximately 60% of classes at MIT having fewer than 20 students. The popularity of this course has reached outside of the MIT campus as a result of the MIT OpenCourseWare initiative. This is seen in a comment by Bill Gates who told the Seattle Post-Intelligencer "Everybody should watch chemistry lectures -- they're far better than you think. Don Sadoway, MIT -- best chemistry lessons anywhere. Unbelievable".
Sadoways lectures often included the history of science, especially with respect to the Nobel Prize. Sadoway gave out "library assignments" in which he asked students to research Nobel Prize–winning papers. He began his lectures by playing music, which has some connection with the lectures material. For example, for the lecture on hydrogen bonding he plays Handels Water Music. For one of the lectures on polymers he plays Aretha Franklins "Chain of Fools". He ended his lectures with five minutes on the topic of "chemistry and the world around us". Examples include automotive exhaust catalytic converters (technology), forensic examination of paintings (chemistry in the fine arts), the mistreatment of Rosalind Franklin in the quest to discover the structure of DNA (intellectual dishonesty), the metallurgical failure that sank the Titanic (greed and incompetence), and the clarification of champagne (viticulture).