The 61-year-old Grammy-winning guitarist will perform at The Joint at Hard Rock Hotel & Casino under a multi-year deal with AEG Live.
Through 2010, The Joint will be the only place west of the Mississippi where fans can see Santana perform.
"Supernatural Santana: A Trip Through the Hits" will debut May 27, featuring the artist's "signature fusion sound in a show designed exclusively for the new venue," AEG Live said in a news release.
"Bringing Santana to The Joint at Hard Rock elevates the entertainment options in Las Vegas," John Meglen, president and co-chief executive officer of AEG Live/ Concerts West, said in a statement.
AEG Live previously has signed Celine, 41, Elton John, 62, Cher, 62, and Bette Midler, 63, to similar residency deals at The Colosseum.
"The Hard Rock Hotel & Casino is thrilled to be the first to house a true rock resident show at our brand-new, state-of-the-art venue The Joint," added Randy Kwasniewski, president and chief operating officer of Morgans Hotel Group Las Vegas and Hard Rock Hotel & Casino.
Copyright 2009 by United Press International.