American Taylor Fritz shocked No. 1 seed and tournament favourite Guido Pella 6-4, 3-6, 6-4 to advance to the quarterfinals at Eastbourne on Wednesday.
Fritz, who broke Pella's serve to seal the deciding set, will face Hubert Hurkacz in the last eight after he defeated Sam Johnson 6-3, 7-6 (6).
There was also success for former U.S. No. 1 Sam Querrey after he defeated No. 4 seed Dusan Lajovic 6-2, 6-3.
Querrey will play former Wimbledon quarterfinalist Fernando Verdasco in the next round after the Spaniard fought from a set down to beat Juan Londero 6-7 (4), 6-3, 7-6 (2).
Elsewhere, British No. 1 Kyle Edmund defeated fellow countryman Cameron Norrie 6-2, 6-2.
Edmund will face another Brit in the next round in Dan Evans, who defeated Pierre-Hugues Herbert 6-3, 7-5.
Gilles Simon won 6-2, 6-4 against Nicolas Jarry and will play Thomas Fabbiano, who upset No. 2 seed Laslo Djere 7-6 (5), 7-6 (6) to advance.