Middlesex County Kennel Club began as the Toy Dog Club of New England (TDCNE).

Organized on June 15, 1910, TDCNE held their first Bench (Conformation) Show under the rules of the American Kennel Club (AKC) on Saturday, May 31, 1913 at the Brooklawn Pavilion in New Bedford, MA.

At that time the club President was Mrs. S. Beswick of Fall River (Pomeranians), First Vice President (and Delegate to the AKC) was Mr. Henry T. Bowers of Dorchester (Boston Terriers), Second Vice President was Mrs. Hattie E. Anderson of Dorchester (English Toy Spaniels), Third Vice President was Mr. F. L. Parnham of Jamaica Plain (Yorkshire Terriers), Secretary was Mrs. M. P. Bowers of Dorchester (Boston Terriers), and Treasurer was Mr. R. Hodson, Jr. (address and breed unknown). Fourteen members comprised the Bench Show Committee including two members, Mr. and Mrs. Frank T. Eskrigge of Newton Centre, who would be very involved with the club for many years to come.

Mr. Frank T. Eskrigge was President of the TDCNE on April 5, 1921 when the majority of members present at a regular meeting of the club, held at the Copley Square Hotel in Boston, voted to rename the club Middlesex County Kennel Club, broadening the scope of the club for breeds of all sizes, and reducing the club home geography to an area that the AKC could protect from competition by other dog clubs events. The first Bench Show held under the new name was actually the ninth show organized by the members of the club. This occurred only two weeks later, on Tuesday, April 19, 1921, at Malta Temple Hall in Cambridge.

At the time of the change, the AKC was in the process of assigning breeds to each of five Groups for competition at dog shows, which was completed by 1923 and went into effect in 1924. According to the AKC's Schedule of Points for the East Division, adopted May 7, 1919, the most popular breed in the area by far was Boston Terriers. To earn 3 points toward a championship, a minimum of 50 Boston Terriers was needed in competition at that show. Several members of TDCNE owned Boston Terriers, which was assigned not to the new Toy Group but rather to the new Non-Sporting Group. Other popular breeds in the area were larger than a toy size, including: Airedale Terriers (35+ dogs needed in competition for 3-points), Shepherd Dogs (25+ dogs), Cocker Spaniels (22+ dogs), and French Bulldogs (20+ dogs). It can be presumed that by eliminating the toy dog emphasis more dog breeders and owners would be interested in joining the club. In fact, Mr. and Mrs. Frank T. Eskrigge owned Cocker Spaniels, a breed assigned to the new Sporting Group.

Middlesex County Kennel Club's (MCKC) all-breed conformation shows were held in either Cambridge or Newton for several decades, until moving to locations in Concord through the 1950's, 1960's, and early 1970's. In 1974 the show (on June 16) moved to Chelmsford where it was held until the late 1980's when it moved around to different locations (Lexington, Westford, Hopedale) before settling at the Minuteman Regional Vocational Technical High School in Lexington for several years, and then at the Topsfield Fairgrounds. Since 2016 the show has been held at the Schooling Grounds in South Hamilton.

From 1985 through 2011 MCKC hosted a second show annually, which was included in the 4-day Bay Colony Cluster of Dog Shows held in the fall. Beginning at the Bayside Exposition Center in Boston, the Cluster moved to Providence, RI for the shows from 2009 to 2011.

In 2009 MCKC began a new venture for the club, hosting Agility Trials in addition to the annual all-breed conformation show.