Shadow education minister Rushanara Ali has stood down from the party front bench, amid a dramatic vote to authorise military action against Isis.
The Labour MP resigned so she could vote against military intervention in Iraq, but the plans were backed by 524 votes to 43, giving the government a majority of 481.
Around 70 MPs are thought to have been absent.
"I am unable in conscience to support the motion," she wrote to Ed Miliband.
He replied: "I know that you have thought long and hard about this. I respect and accept your resignation."
Labour MP Iain Mckenzie was also sacked as aide to Vernon Coaker for voting against military action.
The vote does not authorise action in Syria but allows the UK to participate in air strikes against Isis in Iraq, where the government has requested British help.
Some legal experts believe that may be a difficult distinction to maintain, as any action spilling over into Syria could allow British airplanes to follow the enemy.
Military action could take place as soon as this weekend. The US is currently taking the lead in military operations with five Middle East Sunni-led states.