Start with the 13:55 Lufthansa flight from Istanbul to Frankfurt, about 3h 10m. Transfer in Darmstadt central, then take the 20:15 FlixBus bus on to Frankfurt central (30 min). Transfer in Frankfurt central, then take the 07:30 (+1d) FlixBus bus on to Luxembourg (3h 10m). You arrive in Luxembourg around 10:40 (+1d). In total it's roughly EUR 140 over 15h 50m, 2 transfers.
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Opens Omio — enter your date to compare trains and buses for this route; the price is finalised at checkout.
Fly into Darmstadt central, then continue to Luxembourg by bus (30 min) — routing via Darmstadt central keeps the trip simple. Flight (Lufthansa, 3h 10min) + Bus (FlixBus, 30min) via Darmstadt central + Bus (FlixBus, 3h 10min) via Frankfurt central.