Lambie replaces Johan Goosen, who started at 10 in last month's 32-16 Rugby Championship defeat by New Zealand in Soweto.
Wing JP Pietersen and lock Juandre Kruger replace Bryan Habana and Andries Bekker respectively, while Saracens hooker Schalk Brits features on the bench.
"I'm excited to see what Pat can bring to the team," Springbok coach Heyneke Meyer said.
"He played very well in the last few weeks of the Absa Currie Cup and hopefully he can bring that momentum with him on Saturday.
"It's also good to have JP back. He's had a great season and will want to finish the season on a high.
"At lock there has been strong competition for the number five jersey all season and now Juandre gets an opportunity again."
The free-running Brits - a star of the Aviva Premiership - has returned to Springbok fold for the first time since 2008.
"Schalk is an explosive player who can add something special from the bench," said Meyer.
South Africa have headed to Europe with a lengthy injury list that includes Schalk Burger, Juan Smith and Heinrich Brussow.
Meyer views the tour as an opportunity to begin building a squad for the 2015 World Cup, which is being hosted by England.
"I want to see which of the players can handle the northern hemisphere conditions as it will be the same for 2015," he said.
"We'll be facing an Ireland team that is never an easy opponent in Dublin.
"The Springboks have only won one of their last four Tests here and since they lost at Aviva Stadium against South Africa in November 2010, Ireland have recorded a number of good victories at their home ground.
"They are a quality and well-balanced side with good experienced players.
"We've seen in our last number of Tests against Ireland how dangerous they can be."
South Africa: Z Kirchner (Blue Bulls), JP Pietersen (Sharks), J Taute (MTN Golden Lions), J de Villiers (Western Province, capt), F Hougaard (Blue Bulls), P Lambie (Sharks), R Pienaar (Ulster), T Mtawarira (Sharks), A Strauss (Cheetahs), J du Plessis (Sharks), E Etzebeth (Western Province), J Kruger (Blue Bulls), F Louw (Bath), W Alberts (Sharks), D Vermeulen (Western Province).
Replacements: S Brits (Saracens), CJ van der Linde (Golden Lions), P Cilliers (Golden Lions), F van der Merwe (Blue Bulls), M Coetzee (Sharks), M Steyn (Blue Bulls), J de Jongh (Western Province), L Mvovo (Sharks).
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