Former Bayern Munich midfielder came on as a substitute in the 62nd minute, replacing Brazilian striker Edu.
Kaiserlautern beat Schalke 1-0 thanks to a goal from Lakic in the 42nd minute. It was Karimi’s first performance in Bundesliga since he joined the German club in the winter transfer window.
Schalke is scheduled to play Manchester United in the UEFA Champions League on Tuesday at the Veltins Arena.
Karimi's last Bundesliga game had taken place in June 2007 when he scored his third and final Bundesliga goal for Bayern Munich against Mainz 05, according to Persian Football.
The Iranian had already played for Schalke in the final six minutes against Inter Milan in the Champions League quarterfinal.
Schalke is 10th in Bundesliga standings table and will concentrate on the Champions League and the German Cup final instead.