Spain suffered a 2-1 defeat at the hands of Slovakia, while England cruised to a 5-0 victory against San Marino in Thursday's round of 2016 Euros qualifying fixtures.
Following their convincing 5-1 win over Macedonia in their opening Group C qualifier, Vicente Del Bosque's side could not continue their winning ways as they were defeated by Slovakia at the Stadion MSK Zilina.
Juraj Kucka's early strike was cancelled out by Paco Alcacer in the closing stages of the match, before Miroslav Stoch grabbed the winner for Slovakia right at the death.
Although the match began with Spain dominating possession, it was the hosts who got the first chance of the game as Robert Mak forced Casillas into a brilliant one-handed save in the 11th minute.
At the other end, Diego Costa and Cesc Fabregas, who have been brilliant for Chelsea this season, created Spain's first chance in the 14th minute as the former narrowly headed wide after getting at the end of the latter's cross.
This miss proved to be costly for Spain as Slovakia broke the deadlock through Kucka in the 17th minute. Kucka fired a 30-yard freekick straight down the middle but Casillas misjudged the ball and dived to the right, allowing the hosts to take the lead.
Spain began to bombard the host's defence with continued attacks in the latter stages of the first half, but Slovakia goalkeeper Matus Kozacik made some top-class saves to deny the likes of Andres Iniesta, Costa and Sergio Busquets.
After the break, the visitors continued searching for an equaliser as Kozacik made another save to deny Fabregas.
Costa also took a shy at goal in the 52nd minute but Kozacik again stood up to the task as he kept out a low effort from the striker.
Spain finally managed to beat Kozacik and level the score in the 82nd minute through substitute Alcacer, who, after coming in for David Silva, fired home from 12 yards following a good pass from Jordi Alba.
However, Spain's joy was short-lived as the hosts grabbed the winner through Stoch with only three minutes remaining on the clock. Marek Hamsik sent in a brilliant cross towards Stoch, who made no mistake as he headed home from close range.
Meanwhile, England recorded their second straight win the 2016 Euro qualifiers following a convincing 5-0 win over San Marino.
Goals from Phil Jagielka, Wayne Rooney, Danny Welbeck and Andros Townsend coupled with an own goal from Alessandro Della Valle proved too much for San Marino, who were not even able to score a consolation.
The game started with England on the attack as Wayne Rooney tested San Marino goalkeeper Aldo Simoncini with a freekick, before Danny Welbeck's goal-bound effort flew wide after taking a deflection off Jagielka.
The Three Lions soon took the lead in the 24th minute through Jagielka, who headed into an empty net after Simoncini made a mess of James Milner's corner.
England doubled their lead just before the break through a penalty, which was awarded following Andy Selva's high footed challenge on Rooney. The Manchester United captain stepped up and smashed the ball into the top right corner of the net.
After the break, Hodgson brought on Alex Oxlade-Chamberlain and the Arsenal man made an immediate impact as he pick out fellow Gunner Welbeck, who found the net from close range.
Things went from bad to worse for San Marino as England scored their fourth goal of the night in the 72nd minute through Andros Townsend, who cut in from the right flank before firing a low effort past Simoncini.
Finally England sealed the game in the 77th minute through an own goal from Della Valle, who turned the ball past his own goalkeeper while trying to clear a cross from Rooney.
Other Results: Belarus 0-2 Ukraine, Macedonia 3-2 Luxembourg, Lithuania 1-0 Estonia, Slovenia 1-0 Switzerland, Liechtenstein 0-0 Montenegro, Moldova 1-2 Austria, Sweden 1-1 Russia.