O'Connell, the 2009 Lions tour skipper in South Africa, takes over from flanker Sam Warburton, who rests a knee injury.
The team contains nine Welshmen, including the entire back-row of Dan Lydiate, Justin Tipuric and Toby Faletau.
The match-day 23 features 17 players who are on their first Lions tour.
Lions head Coach Warren Gatland said: "I am really excited by the first selection of the tour.
"Naturally, it comprises largely those players not involved in last weekend's Aviva Premiership and RaboDirect PRO12 finals, and we have a lot of players making their debuts for the Lions.
"At the same time we have a hard core of experience, with six former Lions sharing 430 caps between them and 19 Lions Tests.
"There are also some proven combinations, such as the Welsh centre pairing and back-row.
"Some of the boys who played last weekend are on the bench as cover, and generally everyone in the camp is raring to go."
Lions manager Andy Irvine added: "After all the pre-tour preparation in Cardiff and Dublin, the match against the Barbarians on Saturday marks another milestone in the proud history of the Lions and the start of the 2013 tour.
"This is the important first match of a 10-match tour, and the players are eager to get the tour off on the right note.
"Training has gone very well, and it is exciting to see 11 players making their run-on debuts for the Lions, including the tour's youngest player Stuart Hogg."
Gatland said that Warburton's absence from the opening game was purely precautionary.
Warburton's Wales colleague Justin Tipuric will wear the number seven shirt on Saturday, having firmly established his credentials during this season's RBS 6 Nations Championship.
"He (Warburton) has had a little bit of a sore knee for the last 10 days," Gatland added.
"The medics have given him an injection and said for him to just stay off it for about five days.
"He was desperate to play, but we just felt so early in the tour it is not worth the risk. It is just precautionary."
O'Connell, meanwhile, wants to see the tour get off to a flying start this weekend.
"I remember the first game we had in South Africa in 2009," he said.
"It was a very tough game. We didn't play fabulously well, but we finished well and got the win. It got us moving in the right direction, and if we can do that this weekend, it will be great.
"The players have completely dived into the whole thing. We are very tight already, and there is a big buzz and excitement about making this tour very special."