The Frenchman walked off the court in the second set of his match against compatriot Pierre-Hugues Herbert, having lost the opener.
In the women's draw, Simona Halep and Karolina Pliskova won their matches in two sets, beating Wang Qiang and Amanda Anisimova, respectively.
Here are some select scores:
(1) Simona Halep beats Wang Qiang: 7-5, 6-1
(5) Karolina Pliskova beats (WC) Amanda Anisimova: 6-1, 7-6 (2)
(31) Philipp Kohlschreiber beats (2) Marin Cilic: 6-4, 6-4
Pierre-Hugues Herbert beats Gael Monfils: 6-2, 3-1*
Cilic had an off-day on Tuesday and the in-form Kohlschreiber capitalised, setting up a meeting with Herbert in the next round.
The second seed double-faulted early, setting the tone for a bad day at the office. Kohlschreiber―who entered the match with an excellent 6-4 record against Cilic―put pressure on the Croat's serve early and often, and it paid big dividends, especially in the second set.
Monfils didn't enjoy a great outing, either, as shared by the tournament's official Twitter account:
The Frenchman had already been involved in an epic match with John Isner that left both players drained once it was over. He never found a rhythm against Herbert, with his back clearly bothering him, and a retirement was probably the right decision.
Both Herbert and Kohlschreiber find themselves in a fantastic situation―with Cilic following a host of other top seeds out of the tournament, the road to the semi-finals appears wide open. The bottom half of the draw is devoid of serious star power, and one of Juan Martin del Potro and David Ferrer will also go out after they meet on Tuesday.
In the women's draw, the early action was dominated by Halep:
The top seed had to dig deep to get past Wang in the first set, but once she claimed the advantage, she cruised to the finish line, improving her level as she went along.
Elsewhere, fans caught an unusual spectator for the contest between Pliskova and Anisimova:
The 16-year-old Anisimova beat Petra Kvitova in the previous round, ending her 14-match win streak, but her Cinderella run came to a swift end against an unleashed Pliskova.
The teenager did flash her talent in the second set but never seemed likely to score an upset in the tie-break.