The Scot succeeded Paolo Di Canio on March 1 and took Town to the semi-finals of the League One play-offs, where they were beaten on penalties by Brentford.
According to local reports, he missed Friday's friendly against Forest Green for "personal reasons".
And the club released a statement on Saturday which read: "Swindon Town can confirm that, after further meetings with the Board of Directors today, Kevin MacDonald has left his position as First Team Manager by mutual consent.
"The Club would like to thank Kevin for all his hard work during his time at Swindon Town and wish him all the best for the future.
"Kevin would also like to thank the Directors, staff, players and supporters for the backing and support they have given him over the last few months.
"The process to find a replacement for Kevin will begin immediately and Mark Cooper will be placed in temporary charge of the team until that process is complete."