Jose Mourinho left Didier Drogba on the bench, with Eidur Gudjohnsen handed a starting spot, while Paulo Ferreira returned at right-back and William Gallas moved to left-back.
Betis made a strong start, with Chelsea finding themselves having to defend for the opening few minutes.
However, Arjen Robben began to stretch the home defence on the Chelsea left, before Betis were forced into two substitutions due to injuries to left-back Nano and striker Ricardo Oliveira.
Dani took over from the latter and he broke the deadlock with 28 minutes on the clock, as Alberto Rivera slid the ball in from the left, Edu stepped over it and Dani was left with time to slip his shot under Petr Cech from six yards.
Joe Cole had a chance to level seven minutes before the break, but he fired his shot straight at Pedro Contreras following a neat through ball from Gudjohnsen.
Robben tested Contreras soon after with a drive from the edge of the area, before Gudjohnsen wasted the best chance of the half after being sent clear by John Terry.
Dani almost doubled the lead right on half-time, but fired wide of Cech's left-hand post.
Drogba and Shaun Wright-Phillips were introduced at the interval and the Blues immediately looked more lively than they had done before the break.
However, they failed to seriously test Contreras, while becoming increasingly frustrated by the histrionics of some of the Betis players.
Damien Duff entered the fray just past the hour mark for a subdued Robben and 19 minutes from time the Irishman's cross caused mayhem in the home area.
Drogba just failed to make contact, Wright-Phillips pulled the ball back from the by-line and Michael Essien's effort came back out off both posts before being gathered by Contreras.
Both sides had five players booked, with the game seeing a number of confrontations that Luxembourg referee Alain Hamer failed to get under control.
That led to a frantic finish to the game, with Betis hanging on for victory after three added minutes.