"Two men had inappropriate relationships with two younger women, who work in the AFL industry," McLachlan said.
"The AFL that I want to lead is a professional organisation based on integrity.
"I expect my managers to be role models and set a standard for the rest of the organisation. They are held to a higher standard.
"I want a diverse and inclusive culture, where employees are treated respectfully and fairly at all levels.
"It must be backed up with action and change."
McLachlan said numerous parties were involved in this situation and asked the media to respect their privacy.
He also said it was "commendable" that Lethlean and Simkiss had taken responsibility for their actions.
Lethlean and Simkiss were both newly promoted, assuming their roles in early March.
Andrew Dillon will take over the role of General Manager of Football and Darren Birch becomes General Manager of Commercial.
McLachlan said the only concerns about Lethlean and Simkiss had been brought to his attention by the men themselves, rather than from other parties.
He denied the AFL has a culture problem, but said he would continue striving to ensure the organisation meets the standards expected of it by the community. McLachlan also said there were "no excuses" for poor behaviour.
The Herald Sun reported at least one affair was an open secret in the office and when confronted by a friend of one of the women involved, one manager yelled at her, leaving her in tears.