The pair will return on the bench, with Queensland also making two changes to their starting XV.
Harry Hockings will start at lock, with Lukhan Salakaia-Loto shifting to flanker, while Angus Scott-Young will start at No.8 with Caleb Timu on the bench.
Izack Rodda will also play, determined to help the Reds try and arrest the Crusaders record 17-game winning streak despite the death of his father last week.
With each Super Rugby team having to rest its Wallabies at times in the lead-up to the World Cup, there had been some thought Rodda would take time off this week.
But as he was last week, Rodda was determined to play and the Reds have respected his wishes.
Queensland's backline remains unchanged after causing headaches for the Highlanders in Dunedin.
Coach Brad Thorn said it was good to have Higginbotham and Smith return.
"They bring good experience and provide us with a strong bench," he said.
"Harry (Hockings) has been working hard at training and deserves his spot in the starting side this week."
Attack coach Jim McKay said thought had been given to starting Higginbotham and Smith, given their experience, but the starters had deserved to retain their places after the effort against the Highlanders.
"There were discussions surrounding that but the other guys have done very well and on the back of last week where we played quite well -- obviously we didn't get the result we wanted to -- we needed to recognise and reward that effort," McKay said.
"We're confident in (the starters) but equally, we're confident in the guys coming off the bench and doing a job for us as well."