Blackburn dumped West Ham out of the Carabao Cup as the Championship side triumphed 10-9 on penalties at the London Stadium after a 2-2 draw.
Rovers led through an early goal from Jack Vale before efforts from Pablo Fornals and Michail Antonio turned things around in West Ham's favour.
Substitute Ben Brereton Diaz then netted an 88th-minute equaliser to send the third-round tie to a shoot-out and, after 19 successful spot-kicks, Angelo Ogbonna hitting the bar saw the Premier League side knocked out.
Two top-flight outfits were taken to penalties by League One sides but made it through to round four, in defending champions Liverpool and Southampton.
Liverpool were held to a 0-0 draw at Anfield by Derby, then prevailed 3-2 in the shoot-out, with Caoimhin Kelleher saving three efforts and Harvey Elliott scoring the decisive kick.
Southampton got past Sheffield Wednesday 6-5 after a 1-1 draw at St Mary's, watched from the stands by prospective new Saints manager Nathan Jones.
The hosts, led by interim boss Ruben Selles following Ralph Hasenhuttl's sacking, fell behind to a Josh Windass goal before James Ward-Prowse equalised with a penalty on the stroke of half-time.
Alex McCarthy then saved Dominic Iorfa's spot-kick in the subsequent shoot-out to put Southampton through.
Premier League leaders Arsenal crashed out as Brighton came from behind to win 3-1 at the Emirates Stadium.
After Eddie Nketiah had put the Gunners ahead, debutant goalkeeper Karl Hein, all in one motion, fell over and conceded a penalty with a foul on former Arsenal striker Danny Welbeck, who then beat him from 12 yards to draw things level.
Two subsequent breakaway goals after the interval, from substitute Kaoru Mitoma and Tariq Lamptey, saw Brighton advance.
Manchester City beat Chelsea 2-0 at the Etihad Stadium with Riyad Mahrez and Julian Alvarez striking early in the second half, a game which included England midfielder Kalvin Phillips coming off the bench to make his first appearance since undergoing shoulder surgery in September.
Nottingham Forest won 2-0 at home against Tottenham thanks to a Renan Lodi strike in the 50th minute and a header from Jesse Lingard – his first goal for the club – seven minutes later.
The hosts had to play the final 14 minutes with 10 men after Orel Mangala had been sent off.
Boubacar Traore's late winner saw Wolves defeat Leeds 1-0 at Molineux, while Newcastle progressed with a 3-2 win on penalties over Crystal Palace at St James' Park after a 0-0 draw, with the Magpies' England goalkeeper Nick Pope making three saves in the shoot-out.
Thursday sees round three conclude with Manchester United hosting Aston Villa and the draw for the fourth round taking place.
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