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The club was established by the 2002 merger between Glasgow Southern RFC and Hutchesons' - Aloysians' RFC. The former club was originally known as Clarkston but was renamed in 1995 with the ambition of creating the premier side on the south side of Glasgow. The latter club was also formed as the result of an earlier merger between the former pupils (FPs) clubs of Hutchesons' Grammar School and St Aloysius' College. The merged club is now firmly established as the premier club on the south side of Glasgow.

The club was formed in 1923 playing out of Auldhouse, the school's sports ground in Eastwood (near Thornliebank). Admitted as a full member of the Scottish Rugby Union in 1937, the Hutchesons’ Club entered the National League system in Season 1973 at 2nd Division level, having dispensed with tradition to some degree by opting for "Open" status two years previously, a significant decision forced, by necessity, on many Scottish F.P. Clubs at that time.

1990 was to see further constitutional change when the club agreed amalgamation with close friends and one time rivals to form Hutchesons' Aloysians R.F.C.

By contrast, the Old Aloysians club was formed in 1955 for the sole purpose of undertaking a challenge match against the extremely successful Saint Aloysius' College 1st XV. The unexpected success of this venture resulted in a decision to seek regular fixtures which led to a continuing upsurge in interest and the inevitable and rapid expansion of the F.P. Club. The first fixture was against Hutchesons' Grammar FP RFC., coincident with the invitation from Hutchesons' Grammar School to Saint Aloysius' College 1st XV to undertake regular fixtures. This long standing friendship led to the amalgamation in season 1990–91.

Richard Allan was selected as the club's first full internationalist for the Irish fixture at Murrayfield in 1969, to be followed by other distinguished players who gained representative honours. Brothers Gordon and Alan Bulloch were to gain national caps, with the former captaining the national side on several occasions. Ray Nelson was to achieve caps for the United States national team the U.S. Eagles.

Unlike the two Former Pupil Clubs now involved at Braidholm, Clarkston RFC, since its formation in 1937, had always been an "Open" club, created by a variety of former pupil rugby players who did not wish to undertake cross city travel to indulge in their sport. Significantly the first club chairman was a Glasgow Academical, the first President a Glasgow High former pupil and the longest serving club captain and coach, Andrew Williams a product of Allan Glen's.

Playing initially at the local authority's Overlee ground, years of tireless fund raising saw the club's new facility at Braidholm opened by S.R.U. President Charlie Drummond in January 1971. The club entered the new National League structure in 1973 at 4th Division level, rising through the years to division two. With three pitches, floodlights, 250 seater stand and expanded clubhouse, in recognition of its changing character and by a significant membership majority at the May 1995 A.G.M., the club altered its name to Glasgow Southern RFC.

Over several years a variety of players graduated through the Club participation from both youth and senior level to achieve representative status. Full International caps were awarded to Gordon McIlwham, and Euan Murray while others have achieved selection at Youth level.

Agreement reached with a development organisation saw the original 1970 clubhouse demolished to make way for a health club. A new, state of the art, clubhouse was formally opened by S.R.U. President Ronnie Young at Braidholm in January 2002. The Glasgow Southern name was only to survive for seven years before it became evident to all concerned that the sport on the south side of Glasgow would be best served through amalgamation, an initiative formalised in May 2002 with the formation of Glasgow Hutchesons' Aloysians Rugby Football Club. Plans for an all-weather artificial pitch at Braidholm were announced in 2018.