FA Cup runners-up Stoke City took a step closer to the UEFA Europa League group phase with a 1-0 win over FC Thun, but UEFA Champions League semi-finalists Schalke were stunned 2-0 by Finnish side HJK Helsinki.
Stoke, competing in Europe for the first time since the 1974/75 UEFA Cup, secured a narrow victory at Swiss league leaders Thun thanks to an 18-minute strike from midfielder Danny Pugh.
Thun, who played in the Champions League six years ago, finished the game with ten men and defender Nicolas Schindelholz in goal after goalkeeper David da Costa was sent off in injury time for a last-man foul on Jon Walters.
Victory puts Tony Pulis' side, beaten 1-0 by Manchester City in May's FA Cup final, in pole position ahead of the return leg at the Britannia Stadium next Thursday.
Schalke were dreaming of a Champions League final place four months ago, but Raul and co may have to forgo European competition altogether this season after a shock defeat in the Finnish capital.
HJK boast 40-year-old former Ajax, Barcelona and Liverpool playmaker Jari Litmanen in their ranks, but it was 21-year-old forward Teemu Pukki who did the damage against the Bundesliga heavyweights.
The former Sevilla player opened the scoring in the 18th minute, cutting in from the right flank and unleashing a soaring drive into the far corner with his left foot, before completing his brace in the 54th minute.
Twenty-time Greek champions Panathinaikos also had a night to forget, as they went down 3-0 at Maccabi Tel Aviv, while 2009 Dutch champions AZ Alkmaar fell 2-1 at Norwegian outfit Aalesunds FK.
There were no less than 38 matches scheduled in the Europa League on Thursday, with Tottenham Hotspur, Celtic, Rangers, Atletico Madrid, Sevilla, Lazio, Roma and Paris Saint-Germain among the teams in later action.