Starting for the second time in three days, Buehrle needed two innings Sunday to reach the milestone, but he failed to get through the first against Tampa Bay.
Two errors lead to Buehrle allowing eight unearned runs and five hits over a career-low two-thirds of an inning. He had gone 6 2-3 innings Friday night en route to his 15th win.
Tampa Bay's first run scored when first baseman Edwin Encarnacion dropped Steven Souza Jr's soft liner for the Blue Jays' second error in five batters.
Tim Beckham drew a two-out bases-loaded walk and Joey Butler hit a grand slam on an 85 mph offering - the fastest of Buehrle's 45 pitches - to make it 6-0. The slam came after a close call by plate umpire Alfonso Marquez went against Buehrle on a 2-2 pitch.
Manager John Gibbons took Buehrle out after Brandon Guyer's RBI single.