Real Betis piled more pressure on Gennaro Gattuso as AC Milan surrendered top spot in Group F in a listless 2-1 home loss in the Europa League.
Giovani Lo Celso set up Antonio Sanabria's 30th-minute opener and curled in a wonderful sealer 10 minutes after the interval to fire the LaLiga side ahead of their hosts, who are now only two points clear of third-placed Olympiacos.
It was no worse a fate than Milan deserved for waiting until the 83rd minute to issue any kind of riposte to their weekend defeat to city rivals Inter.
Samu Castillejo teed up Patrick Cutrone to reduce the deficit and the winger was unfortunate not to win a penalty late on, his frustration boiling over in a late lunge on Lo Celso that earned a straight red card.
Pepe Reina, standing in for Gianluigi Donnarumma, began an unconvincing performance with a loose pass from the back in the third minute that Sanabria failed to punish.
Not discouraged, the Paraguay striker made amends with a tap-in served to the near post by Lo Celso.
Betis could have been out of sight before the break but a contentious offside decision cost Sanabria a second before he shanked a promising volley.
Their sense of injustice grew as Reina used a combination of chest and arm to deal with a ball outside his box, although a let-off did come when Gonzalo Higuain's tentativeness invited Aissa Mandi into a last-ditch challenge with the goal gaping.
There was nothing any goalkeeper could have done about Lo Celso's classy 55th-minute strike, the midfielder spectacularly curling in off the left post from 25 yards.
Castillejo crashed a shot against the upright soon after and, after supplying the pass that substitute Cutrone tapped home in the 83rd minute, was well within his rights to question a challenge from Marc Bartra that could have spared Gattuso from fresh scrutiny, but a poor tackle in stoppage time that prompted his dismissal was hardly the right method of protest.
What does it mean? Gattuso feeling the heat
Milan will be loath to jettison a favoured son who gave them so much on the pitch but, amid rumours sporting director Leonardo is lining up an approach for free agent Roberto Donadoni, this uninspiring performance came at a terrible time for the under-fire Gattuso.
Lo Celso the heartbeat for Betis
Lo Celso's surprise off-season loan switch from Paris Saint-Germain to unheralded Betis seems well and truly justified on the evidence of his display at San Siro, the Argentina international responsible for almost everything his team created in an attacking sense.
Reina fails to shine on first-team audition
Gattuso's resolve to resist supporter calls for Reina to replace Gianluigi Donnarumma in Serie A will only have been strengthened after watching the former Liverpool and Napoli goalkeeper fail to offer the kind of assurance expected from a veteran.
Milan will be expected to secure a result at home to Sampdoria on Saturday as Betis seek to stop a two-match LaLiga losing run with Sunday's trip to Getafe.