The show is fairly close to real life - especially in the large strokes of the series plots. There were obviously creative departures both to add to storytelling but also to protect the identities of some real-life characters. There are several articles that detail fact and fiction - here are three that I thought did a good job:
- The article here does a pretty good job of laying out fact versus fiction following season 1. Among the fictions cited in the article, Barton Scully, Washington University Provost in the show, a fictional character, was gay - the real provost of Wash U. at the time was not gay, but there was someone from the University that was gay which may have influenced the character.
Masters and Johnson did both participate in the early sex studies. Masters did have low sperm count but was able to conceive with his first wife. Prostitutes were involved in the early studies and Masters and Johnson did eventually get married.
- This season three fact vs. fiction article notes that Masters and Johnson did NOT treat a gorilla at the St. Louis Zoo. They also did not have babies after they started their work each had 2 older children - this article details the decision to add babies to protect the real-life characters that the show featured who are still alive.
The real life duo did conduct a scent study to augment their practice's income.
- This Bustle article cites that Virginia Johnson did have sex with Dr. William Masters on several occasions inside study, but that she felt she had to to keep her job and it wasn't romantic as depicted in the show. Their marriage was mostly for business reasons and their divorce essentially ended with their practice.
This infographic summarizes some of these facts and fictions: 
