Andi McElnea's side produced their most disappointing display of the season as their unbeaten record was brought to an end emphatically by the only team which could yet pip them for the Borland Trophy.
Clydesdale were dominant throughout a surprisingly one-sided encounter. Batting first, the Glasgow side took the attack to the home bowlers almost from the start and solid contributions throughout meant they were always likely to register a big total. Paddy Barbour led the way with a hard-hitting 21 before the main substance to the innings was provided by Con de Lange and Sam Page.
De Lange made a series of boundaries on both sides of the wicket before he fell for 72 off the bowling of Callum Leck.
However, the South African-born player's effort was eclipsed on this occasion by Page. He top-scored with 83 - his highest score of the season. There were also useful contributions from Richie Berrington (31) and Mo Awais (29) as Clydesdale powered their way to 264-5.
The Titwood club could yet win the title if they beat Drumpellier on Saturday and Ayr lose in Dumfries.
Elsewhere, with 49 runs and five wickets, former Clydesdale player Harmanjit Singh helped East Kilbride to a 66-run win over Uddingston, while Drumpellier were consigned to the wooden spoon after going down heavily to West of Scotland.
Scott Beveridge also hit a fine unbeaten 41 as Dumfries edged out Renfrew by just one wicket to secure a win at King George V Playing Fields. Beveridge had earlier claimed four wickets to help dismiss the hosts for 162.