The Liverpool midfielder suffered a hamstring injury during the Capital One Cup victory over Notts County and has withdrawn from Chris Coleman's squad.
Coleman was already missing Swansea left-back Neil Taylor (thigh), and the Wales boss has added Sunderland midfielder David Vaughan and Taylor's Swans' team-mate Jazz Richards to his squad for the Group A double-header.
A statement on the Football Association of Wales website read: "Liverpool's Joe Allen will be forced to miss the FIFA World Cup qualifiers against Macedonia and Serbia.
"Allen was injured playing for his club against Notts County at Anfield on Tuesday night in the Capital One Cup.
"He joins Swansea City's Neil Taylor on the sidelines."