Mom and I knew something was up when we didn't see Amanda Blake's name and photo on the opening credits (newer ones than the oval ones). No matter why she wasn't on the show, it is a tragedy: she was a major character who needed to stay.

I have read in many publications that she was so distraught over the death of Glenn Strange, that she didn't think she could handle a season without him. They had become quite close friends. Not sure if we'll ever REALLY know why she left?

According to the definitive (my description) "Gunsmoke" book, published in 1990
authored by Gabor Barabbas, Amanda said that she left of her own volition,
but was anxious to return for any made-for-television movie sequels. She said
she was commuting from Phoenix, Arizona during her final years with the show
and was "just so tired."
Of course, reading between the lines she could have been "just so tired" of all
the disagreements with John Mantley, so Goldie3705's assessment could certainly
be true. I think that Mr. Mantley could have certainly listened to input from
Amanda after playing Kitty for all those years. She certainly had the right
to her opinion of what Kitty was and possibly could be. No character wears the
same clothes for twenty years, and/or remains exactly the same for twenty years.

Kitty was Matt's woman and they never kissed on television. Both Amanda Blake and James Arness have said Matt and Kitty had a physical relationship but both of them and TPTB chose to keep a mystery around Matt and Kitty's relationship, believing that any kind of domestic relationship for Matt would change the tone of the show.
At the end of the 19th season, Amanda Blake was fired by EP John Mantley. They had disagreed over many things for years and when she requested new costumes for the 20th season, he chose to let her go rather than acquiesce. He later said in an interview that letting her go was the biggest mistake of his career. BTW, scripts for the 21st season had already been commissioned and the part of Miss Kitty was included in those scripts so they had reached an agreement that she would return.
She made the rounds of interviews and talk shows saying she had chosen to leave because CBS asked her to do that (do the press), fearing fans of the show would be angry to find out Kitty had been fired. She agreed to do that and took heat from fans for "leaving." To this day, most people will stick to the party line that she left but that is nowhere near the truth.
Sometimes nothing is a pretty cool handLuke Jackson