Villarreal coach Victor Munoz became the first managerial casualty of the season in Spain following his side's 2-1 loss to Hercules but Racing Santander, Real Sociedad, Rayo Vallecano and Espanyol also suffered embarrassing defeats.
Madrigal's hat-trick gave Novelda their incredible 3-2 victory over Barca, although the Catalans can point to the fact they had three goals disallowed, with Xavi's 95th minute 'equaliser' one of those chalked off.
Louis van Gaal thundered: "We have not made this ridiculous situation," whilst Frank de Boer was heavily critical of Robert Enke, who was making his debut in the Barca net.
De Boer claimed that Enke: "Was in a nervous state and that affected all of us at the back."
Rayo lost 2-1 to Cultural Leon, whilst Real Sociedad fell 3-1 to Zaragoza, who were relegated last year as Valery Karpin was sent off for the Basque side.
Alicante beat Espanyol 1-0, whilst Santander, featuring Pedro Munitis could only manage a 3-2 loss to Real Union.
Real Madrid mananged to fall a goal behind to San Sebastian but countered by putting eight past their opponents, Tote and Javier Portillo completing hat-tricks.
Atletico Madrid beat Lanzarote 2-1 with a Jose Movilla goal ten minutes from time avoiding an extra period of play.
Deportivo put their poor start to the season behind them, edging a 2-1 win over Corralejo, a third division side.
Both Valencia and Malaga required penalties to beat Tarragona and Extremadura respectively, with Dario Silva seeing red in the 35th minute.
Mallorca were indebted to a last minute goal to beat Gramanet 1-0 and Athletic Bilbao struggled to put away third division side Amurrio. Celta and Valladolid also won by a single goal, although Alaves' 3-1 win over Baracaldo was one of the few comfortable ones of the first round.
Osasuna beat Lemona 3-0, Gaston Casas (pictured) showed he was back to form with an impressive hat-trick in Betis' 3-0 victory, whilst their Seville neighbours mirrored the result, beating Jaen.
The next round will be held on October 9.
