Coach Todd Paytens team led 12-0 at half-time only to be run down by the Rabbitohs in the second half.
The loss leaves Wests Tigers on 30 points and in sixth position. The win keeps Souths in seventh place, one point behind Wests Tigers.
Wests Tigers opened the scoring in the 23rd minute when full-back Kurtis Rowe ran off an inside pass to beat two defenders in an angle run to score next to the posts. Centre Manaia Rudolph converted the try for a 6-0 lead.
Seven minutes later, hooker Manaia Cherrington dived over from dummy half for a 10-0 lead. Cherrington converted for a 12-0 lead. The score stayed that way until half-time.
South Sydney started the second half strongly when winger Ofa Felila scored from a crossfield kick. Centre Aaron Gray failed to convert the try.
The Rabbitohs were in again when hooker and captain Cameron McInnes chased through a grubber kick to score behind the posts for a 12-8 scoreline. Gray converted for a 12-10 scoreline.
South Sydney hit the lead for the first time in the 72nd minute when full-back Alex Johnston scored to give the Rabbitohs a 14-12 lead. Gray converted for a 16-12 scoreline.
Wests Tigers half-back Luke Brooks was placed on report in the 78th minute for a shoulder charge.