I recently redeemed my first 2-for-1 Amex voucher on an open jaw to the US. I checked availability online (for the outbound and inbound seperately), made a note of the itinerary - then rang up to book, in my case on the Silver line.
Very helpful chap at the other end knew exactly what to do and sorted it quickly and efficiently. This included returning to a different UK airport than the origin (INV), for convenience, something I wasn’t sure would be possible on the voucher.