- Leicester City's Harry Maguire earned his 13th England cap on Saturday evening
- The Three Lions were beaten 2-1 by Spain in their first UEFA Nations League fixture
- Wilfred Ndidi, Kelechi Iheanacho, Rachid Ghezzal and Daniel Amartey were in AFCON qualifying action
- Jonny Evans appeared for Northern Ireland in a Nations League defeat by Bosnia & Herzegovina
The Three Lions were ahead on 11 minutes as Manchester United's Luke Shaw found club team-mate Marcus Rashford to slot it past goalkeeper David de Gea, another Red Devils star.
But less than two minutes later, Luis Enrique's visitors were level when Saúl Ñíguez, the Atlético Madrid midfielder, completed a flowing move to restore parity on the scoresheet.
Spain then took the lead as Rodrigo pounced to convert Thiago Alcántara's free-kick beyond Jordan Pickford in the 32nd minute to confirm England's first competitive home defeat since 2007.
Maguire, meanwhile, completed the full 90 minutes for Gareth Southgate's men, doing well to deny the likes of Sergio Busquets, Isco and Marco Asensio, while heading wide late on.
England next face Switzerland at Leicester City's King Power Stadium on Tuesday evening - a fixture supporters can still secure tickets for by visiting TheFA.com/Tickets (8pm BST kick-off).
Elsewhere, Wilfred Ndidi and Kelechi Iheanacho started as Nigeria got their Africa Cup of Nations qualification campaign back on track with a 3-0 win over Seychelles.
Gernot Rohr’s men, who suffered an opening 2-0 defeat by South Africa last summer, went ahead inside 15 minutes through former Fox Ahmed Musa.
Chidozie Awaziem followed up with a second goal for Nigeria just after the half-hour mark and Odion Ighalo struck from the penalty spot in the second half to seal the win.
Northern Ireland, meanwhile, were beaten 2-1 by Bosnia & Herzegovina in their first Nations League fixture at Windsor Park – a match in which Jonny Evans played the full 90 minutes.
Haris Duljević's 36th-minute close-range flick, from Edin Džeko's cross, put the visitors ahead and Elvis Sarić struck on 64 minutes, before Will Grigg narrowed the arrears in added time.
Forward Rachid Ghezzal, who has scored two goals for City so far this season, started for Algeria in their 1-1 draw against Gambia at Independence Stadium, Bakau.
Daniel Amartey’s Ghana, on the other hand, suffered a 1-0 AFCON qualifying loss to Kenya. The Harambee Stars lead before half-time when Nicholas Opoku struck into his own net.
Despite waves from pressure from Ghana, the hosts held on to pull off a surprise result and go level on points in qualification Group F with the Black Stars and Sierra Leone.
Finally, Development Squad midfielder Faiq Bolkiah featured as Brunei sealed a 1-0 ASEAN Football Championship qualifying victory over Timor Leste earlier on in the afternoon.
LCFC.com is the best place for updates of City's international players with daily reports at the end of each matchday over the next week.