Unstable Behavior
Beginning in Season 1, Betty has demonstrated a number of times that she suffers from some level of mental instability. In several episodes, Betty is shown in therapy, talking to a psychiatrist. After talking to Don about one of her sessions, Don calls Betty's doctor and ends the therapy.
In Episode 9 of Season 1 ("Shoot"), there is an incident in which Betty takes a BB gun and shoots her neighbor's pigeons after the neighbor upsets her children by telling them that if he sees their dog in his yard again, he will shoot it.
Divorce from Don
After years of struggling with Don's infidelity, she meets Henry Francis, an advisor to NY governor Nelson Rockefeller, at
Roger Sterling's Kentucky Derby party (Season 3 Episode 3). They develop a friendship, and eventually, Henry tells Betty that he is willing to marry her. At the end of Season 3, Don and Betty agree to divorce despite the recent birth of their third child, Eugene. The season's final scene shows Betty, Henry and Eugen flying to Reno.
Marginalization
Betty is seen very little in Season 4. She has married Henry, and they live with the three children in the home she shared with Don (which Don still owns). The times when she is shown, she is often unhappy, typically in response to seeing Don move on with his life. By the end of Season 4, Betty is dissatisfied with her marriage to Henry, and it is alluded to that she wants to reconcile with Don.